生物非键模体
|
摘要
按照经典中心法则的定义,生命体内遗传信息是由DNA经RNA流向多肽序列。近年来随着人们对分子生物世界的深入认识,该信息流经途径得到了进一步扩展,即新生肽链需要折叠成具有精密构造的三维结构,进而与其他生物分子和／或生物基质发生时空特异性的识别和相互作用,最终实现遗传信息从基因型到表型的映射。可以看到,上述扩增部分所涉及到的关键环节即蛋白质折叠和识别是由可逆的弱化学力所支配的,通常称这些化学力为生物非键作用(biological noncovalent interaction)。本文进一步扩展了生物非键作用的概念,用以描述生物环境中一个或数个非键作用按照一定空间排列模式构成的具有一定功能的有机整体,称之为生物非键模体(biological noncovalent motif)。在此基础上,本文对生物分子中几类长期被人们所忽视的非键模体的结构和性质开展了系统的调查；另外还定义了数种新型生物非键模体,并以理论计算和数据库检索相结合的方式论证了它们的存在性和功能性；最后介绍了一种我们开发的用于在二维页面上示意性描绘蛋白质复合物界面非键模体的分子图形学软件包2D-GraLab。下面对这些工作逐一进行概述：
(1)蛋白质中的含硫氢键(sulfur-containing hydrogen bond):蛋白质中氮和氧原子参与形成的常规氢键曾引起了相关领域研究者的广泛兴趣并进行了深入研究,但由另一类元素即硫所形成的含硫氢键却长期被人们所忽视了。本文对Top500数据库中所有高质量蛋白质晶体结构进行了统计分析,从中获得了大量关于蛋白质含硫氢键的几何和分布信息。研究发现：①含硫氢键的键长通常大于常规氢键、而键角则普遍小于常规氢键,从而表现出较弱的化学力特征。②Met和Cys的硫原子是不良的氢键受体,但是Cys巯基却是中等强度的氢键供体。③处于复杂蛋白质环境中含硫氢键的几何行为更接近于自由状态下小分子系统氧原子——而非硫原子——所成氢键情况。④在某些情况下含硫氢键对蛋白质结构和功能起着重要的作用,如它们可以促成a螺旋、绑定链间残基、微调局部结构、辅助二硫键生成等。⑤Cys巯基可与芳香性p电子形成较为松散的氢键,其键长大于普通含硫氢键,且其巯基氢原子往往正对于芳香环边缘。
(2)蛋白质／配基界面上的氟键(fluorine bond):氟化是当今制药工业常用的一种用于改善先导实体(lead entity)药代动力学性质的手段,然而含氟药物分子亦可通过共价氟原子与靶标蛋白的各类基团发生多样的非键作用以调理二者识别的特异性和亲和力。本文将这些由氟原子直接参与形成的非键作用称为氟键,进而系统调查了大量存在于蛋白质／配基界面上的氟键的几何分布状态以及它们对配基结合的自由能贡献情况。结果表明：①氟键在几何和热力学上表现出类似于上述含硫氢键的表观特征,而在静电机制方面则更接近于卤键而非氢键。②先前他人研究中多次强调的含氟正交多极作用(C-F…C=O)在本文对蛋白质结构数据库(PDB)检索中并不十分突出；与之相对的是,先前多被人们所忽视的非极性氢参与的氟键(C-F…H-C)却被大量发现于蛋白质／配基界面。③MPWLYP泛函和MMFF94力场可以较好地重现高水平氟键键能,故它们可以被考虑用来处理复杂生物氟键系统。④尽管孤立氟键一般较弱,但氟化亦可通过间接的电子效应来影响配基对受体的识别行为。
(3)生物分子中的卤-水-氢桥(halogen-water-hydrogen bridge):业已知道,生物环境中水分子可以通过多重氢键网络与周围基质发生相互作用,从而形成水中介的氢键桥系统。我们进而推测与氢键在能量和方向上具有极高相似性的卤键可以功能性地取代水中介氢键桥中的一个或数个氢键,从而形成我们称之为卤-水-氢桥的生物非键模体。在此基础上,本文通过理论分析和晶体结构检索相结合的方式证实了上述猜想,即这种推定的卤-水-氢桥确实存在于生物分子世界,尽管它们并不十分常见。同时本文还借助数个典型实例指出这些观察到的卤-水-氢桥可以显著影响生物分子结构模式,并功能性调理蛋白质／蛋白质、蛋白质／核酸以及蛋白质／药物配基之间的特异性识别和相互作用。
(4)生物分子中的卤离子桥(halogen-ionic bridge):生物分子中由电中性的水分子和电正性的金属离子分别介导形成的水中介氢键桥和金属配位桥已经得到了生物化学领域的广泛认同和深入研究,由此我们很自然地联想到普遍存在于生理环境的电负性卤素离子是否亦能参与非键桥联系统,并发挥特异性的生物效应?本文将这类由结构化卤离子所介导的桥联系统命名为卤离子桥以强调其与水分子桥和金属离子桥在结构和功能上的相似性。进而我们通过对小的模型系统、真实的生物分子系统以及PDB数据库的详尽理论分析和统计调查有力确证了该类推测的卤离子桥联模体广泛存在于生物分子世界且在诸多情况中发挥了重要的生物学功能。研究还发现卤素离子可以通过离子氢键、离子键、甚至共价键等方式与生物基团发生有效作用,且这些作用的强度显著大于多数见诸于生物体系的常规非键形式。
(5)蛋白质的卤素模体halide motif):卤素模体可视为对卤离子桥的推广它泛指一切迁移到生物分子内部且被固定于亲卤位点的结构化卤离子,以及周围与该离子发生直接或间接非键作用的生物分子基团所构成的一个功能整体。在此基础上本文提出了能量分解分析法energy decomposition analysis)对782个高质量的蛋白质卤素模体所包含的能量成分进行了系统探索,结果发现结构化的卤素模体往往起到稳定蛋白质建筑的作用,且其稳定化自由能贡献与包埋程度成正相关趋势。出乎意料的是,带有一个形式电荷的卤离子主要是通过色散力——而非静电力——来发挥其稳定化效应。这可解释为尽管卤离子可与周围蛋白质基团发生显著的Coulomb吸引作用,但由此获得的有利静电自由能贡献却因形成卤素模体时所伴随的不利静电去溶剂化惩罚而大打折扣了
(6)二维描绘蛋白质复合物界面非键模体：有鉴于蛋白质／蛋白质相互作用在诸多生理和生化过程中扮演了中心的角色,本文为此专门开发了一种二维分子图形学软件包2D-GraLab,用于示意性描绘已知结构蛋白质复合物界面的多样非键模体。该程序提供了图形界面、控制对话框、三维显示窗口等交互方式以便用户使用,并借助一系列业已得到相关领域广泛认可的计算技术和独立程序进行数据处理以确保输出结果的可靠性,进而将所得信息以二维示意图方式加以直观呈现以供研究者观察和分析目标蛋白复合物界面的各类非键作用模式。
The classic view of the central dogma of biology states that "the coded genetic information hard-wired into DNA is transcribed into individual transportable cassettes, composed of messenger RNA (mRNA); each mRNA cassette contains the program for synthesis of a particular protein sequence." With the progress in the field of biology at subcellular level in recent years, however, our notion about the complete pathway of the genetic information-flow is enlarged to cover biomolecular folding and recognition—that are fundamentally dominated by weak, reversible chemical forces, or called biological noncovalent interactions (BNIs). Here, we further extended the concept of BNI to biological noncovalent motif (BNM) as a description of the functional entity composed of one or several BNIs in biological context. In this dissertation, we define, analyze, and demonstrate a series of specific BNMs that are largely underappreciated in the sophisticated biochemical community. In addition, an in-house program called the 2D-GraLab is also described for automatically generating schematic representation of BNMs across the protein binding interfaces.
(ⅰ) Sulfur-containing hydrogen bonds in proteins. Sulfur atoms have been known to participate in hydrogen bonds (H-bonds) and these sulfur-containing H-bonds (SCHBs) are suggested to play important roles in certain biological processes. This study aims to comprehensively characterize all the SCHBs in 500 high-resolution (<1.8 A) protein structures retrieved from the Top500 database. We categorize SCHBs into six types according to donor/acceptor behaviors and then employ explicit hydrogen approach to distinguish SCHBs from those of non-hydrogen bonding interactions. It is revealed that sulfur atom is a very poor H-bond acceptor, but a moderately good H-bond donor. In a-helix, considerable SCHBs are found between the sulphydryl group of cysteine residueⅰand the carbonyl oxygen of residueⅰ-4, and these SCHBs exert appreciable effect in stabilizing helices. Although for most SCHBs, they possess no specific secondary structure preference, their geometrical characteristics in proteins and in free small compounds are significantly distinct, indicating that protein SCHBs are geometrically distorted. Interestingly, sulfur atom in disulfide bond tends to form bifurcated H-bond whereas in cysteine-cysteine pairs prefer to form dual H-bond. These special H-bonds remarkably boost the interaction between H-bond donor and acceptor. By oxidation/reduction manner, the mutual transformation between the dual H-bonds and disulfide bonds for cysteine-cysteine pairs can accurately adjust the structural stability and biological function of proteins in different environments. Furthermore, few loose H-bonds are observed to form between the sulphydryl groups and aromatic rings, and in these cases the donor H is almost over against the rim rather than the center of the aromatic ring.
(ⅱ) Fluorine bonds at protein-ligand interfaces. Although fluorination of pharmacologically active compounds has long been a common strategy to increase their metabolic stability and membrane permeation, the functionality of protein-ligand interactions involving fluorine atoms, that we named fluorine bonds, was only recently recognized in chemistry and biology communities. Here, the geometrical characteristics and energetic behaviors of fluorine bonds are systematically investigated by combining two quite disparate but complementary approaches:X-ray structural analysis and theoretical calculations. We find that the short contacts involving fluorine atoms between proteins and fluorinated ligands are very frequent and these contacts, compared to those of routine hydrogen/halogen bonds, are more similar to above-mentioned SCHBs. ONIOM-based QM/MM analysis further reveal that fluorine bonds do play an essential role in protein-ligand binding, albeit the strength of isolated fluorine bonding is quite modest. Furthermore, 14 quantum mechanics (QM) and molecular mechanics (MM) methods are performed to reproduce fluorine bond energies obtained at the rigorous MP2/aug-cc-pVDZ level of theory, and results show that most QM methods and very few MM methods perform well in the reproducibility; the MPWLYP functional and MMFF94 force field are recommended to study moderate and large fluorine bonding systems, respectively.
(ⅲ) Halogen-water-hydrogen bridges in biomolecules. The importance of water in biological systems has long been recognized in the field of biology. Here, we describe a new manner by which water affects biomolecular behaviors, called halogen-water-hydrogen bridge (XWH bridge), that is, one H-bond in water-mediated H-bond bridge is replaced functionally by a halogen bond (X-bond). Although behaving similarly to water-mediated H-bond motif, the XWH bridge usually stands in multifurcated forms and possesses stronger directionality. QM analysis on several model and real systems reveals that the XWH bridges are more thermodynamically stable than other water-involved interactions, and this stability is further enhanced by the cooperation between X-bond and H-bond. Crystal structure survey clearly demonstrates the significance of XWH bridges in stabilization of biomolecular conformations and in mediation of protein-protein, protein-nucleic acid, and receptor-ligand recognition and binding.
(ⅳ) Halogen-ionic bridges in biomolecules. If considering that the pronouncedly charged halide anions are ubiquitous in the biological world, then it is interesting to ask whether the halogen-ionic bridges—this term is named by us to describe the interaction motif of a nonbonded halogen ion with two or more electrophiles simultaneously—commonly exist in biomolecules and how they contribute to the stability and specificity of biomolecular folding and binding? To address these problems, we herein present a particularly systematic investigation on the geometrical profile and energy landscape of halogen ions interacting with and bridging between polar and charged molecular moieties in small model systems and real crystal structures, by means of ab initio calculation, database survey, continuum electrostatic analysis, and hybrid QM/MM examination. All of these unequivocally demonstrate that this putative halide motif is broadly distributed in biomolecular systems (>6000) and can confer a substantial stabilization for the architecture of proteins and their complexes with nucleic acids and small ligands. This stabilization energy is estimated to be generally more than 100 kcal·mol-1 for gas-phase state or about 20 kcal·mol-1 for solution condition, which is much greater than that found in sophisticated water-mediated bridge (<10 kcal·mol-1) and salt bridge (～3.66 kcal·mol-1).
(ⅴ) Contribution of halide motifs to protein stability. Halide anions are traditionally recognized as the structure maker and breaker of water to indirectly influence the physicochemical and biological properties of biomacromolecules immersing in electrolyte solution, but here we are more interested in whether they can be structured in protein interior, forming that we named halide motifs, to stabilize the protein architecture through direct noncovalent interactions with their context? In the current work, we present a systematical investigation on the energy components in 782 high-quality protein halide motifs retrieved from the Protein Data Bank (PDB), by means of the continuum electrostatic analysis coupled with non-electrostatic considerations as well as hybrid QM/MM examination. We find that most halide motifs (91.6%) in our dataset are substantially stabilizing and their average stabilization energy is significantly larger than that previously obtained for sophisticated protein salt bridges (-15.16 vs.-3.66 kcal·mol-1). Strikingly, non-electrostatic factors, especially the dispersion potential, rather than the electrostatic aspect, dominate the energetic profile of the pronouncedly charged halide motifs, since the expensive cost for electrostatic desolvation penalty requires to be paid off using the income receiving from the favorable Coulomb interactions during the motif formation. In addition, all the energy terms involved in halide motifs, regardless of their electrostatic or non-electrostatic nature, show to highly depend on the degree of motif's burial in protein, and the buried halide motifs are generally associated with a high stability.
(vi) 2D depiction of interfacial NBMs for protein complexes. A program called the 2D-GraLab is described for automatically generating schematic representation of diverse NBMs across the protein binding interfaces. The input file of this program takes the standard PDB format, and the outputs are two-dimensional PostScript diagrams giving intuitive and informative description of the protein-protein interactions and their energetics properties, including hydrogen bond, salt bridge, van der Waals interaction, hydrophobic contact, p-p stacking, disulfide bond, desolvation effect, and loss of conformational entropy. To ensure the accuracy and reliability of determined interaction information, methods and standalone programs employed in the 2D-GraLab are all widely used in the chemistry and biology communities. The generated diagrams allow intuitive visualization of the interaction mode and binding specificity between two subunits in protein complexes, and by providing information on nonbonding energetics and geometrical characteristics, the program offers the possibility of comparing different protein binding profiles in a detailed, objective, and quantitative manner.
(1)蛋白质中的含硫氢键(sulfur-containing hydrogen bond):蛋白质中氮和氧原子参与形成的常规氢键曾引起了相关领域研究者的广泛兴趣并进行了深入研究,但由另一类元素即硫所形成的含硫氢键却长期被人们所忽视了。本文对Top500数据库中所有高质量蛋白质晶体结构进行了统计分析,从中获得了大量关于蛋白质含硫氢键的几何和分布信息。研究发现：①含硫氢键的键长通常大于常规氢键、而键角则普遍小于常规氢键,从而表现出较弱的化学力特征。②Met和Cys的硫原子是不良的氢键受体,但是Cys巯基却是中等强度的氢键供体。③处于复杂蛋白质环境中含硫氢键的几何行为更接近于自由状态下小分子系统氧原子——而非硫原子——所成氢键情况。④在某些情况下含硫氢键对蛋白质结构和功能起着重要的作用,如它们可以促成a螺旋、绑定链间残基、微调局部结构、辅助二硫键生成等。⑤Cys巯基可与芳香性p电子形成较为松散的氢键,其键长大于普通含硫氢键,且其巯基氢原子往往正对于芳香环边缘。
(2)蛋白质／配基界面上的氟键(fluorine bond):氟化是当今制药工业常用的一种用于改善先导实体(lead entity)药代动力学性质的手段,然而含氟药物分子亦可通过共价氟原子与靶标蛋白的各类基团发生多样的非键作用以调理二者识别的特异性和亲和力。本文将这些由氟原子直接参与形成的非键作用称为氟键,进而系统调查了大量存在于蛋白质／配基界面上的氟键的几何分布状态以及它们对配基结合的自由能贡献情况。结果表明：①氟键在几何和热力学上表现出类似于上述含硫氢键的表观特征,而在静电机制方面则更接近于卤键而非氢键。②先前他人研究中多次强调的含氟正交多极作用(C-F…C=O)在本文对蛋白质结构数据库(PDB)检索中并不十分突出；与之相对的是,先前多被人们所忽视的非极性氢参与的氟键(C-F…H-C)却被大量发现于蛋白质／配基界面。③MPWLYP泛函和MMFF94力场可以较好地重现高水平氟键键能,故它们可以被考虑用来处理复杂生物氟键系统。④尽管孤立氟键一般较弱,但氟化亦可通过间接的电子效应来影响配基对受体的识别行为。
(3)生物分子中的卤-水-氢桥(halogen-water-hydrogen bridge):业已知道,生物环境中水分子可以通过多重氢键网络与周围基质发生相互作用,从而形成水中介的氢键桥系统。我们进而推测与氢键在能量和方向上具有极高相似性的卤键可以功能性地取代水中介氢键桥中的一个或数个氢键,从而形成我们称之为卤-水-氢桥的生物非键模体。在此基础上,本文通过理论分析和晶体结构检索相结合的方式证实了上述猜想,即这种推定的卤-水-氢桥确实存在于生物分子世界,尽管它们并不十分常见。同时本文还借助数个典型实例指出这些观察到的卤-水-氢桥可以显著影响生物分子结构模式,并功能性调理蛋白质／蛋白质、蛋白质／核酸以及蛋白质／药物配基之间的特异性识别和相互作用。
(4)生物分子中的卤离子桥(halogen-ionic bridge):生物分子中由电中性的水分子和电正性的金属离子分别介导形成的水中介氢键桥和金属配位桥已经得到了生物化学领域的广泛认同和深入研究,由此我们很自然地联想到普遍存在于生理环境的电负性卤素离子是否亦能参与非键桥联系统,并发挥特异性的生物效应?本文将这类由结构化卤离子所介导的桥联系统命名为卤离子桥以强调其与水分子桥和金属离子桥在结构和功能上的相似性。进而我们通过对小的模型系统、真实的生物分子系统以及PDB数据库的详尽理论分析和统计调查有力确证了该类推测的卤离子桥联模体广泛存在于生物分子世界且在诸多情况中发挥了重要的生物学功能。研究还发现卤素离子可以通过离子氢键、离子键、甚至共价键等方式与生物基团发生有效作用,且这些作用的强度显著大于多数见诸于生物体系的常规非键形式。
(5)蛋白质的卤素模体halide motif):卤素模体可视为对卤离子桥的推广它泛指一切迁移到生物分子内部且被固定于亲卤位点的结构化卤离子,以及周围与该离子发生直接或间接非键作用的生物分子基团所构成的一个功能整体。在此基础上本文提出了能量分解分析法energy decomposition analysis)对782个高质量的蛋白质卤素模体所包含的能量成分进行了系统探索,结果发现结构化的卤素模体往往起到稳定蛋白质建筑的作用,且其稳定化自由能贡献与包埋程度成正相关趋势。出乎意料的是,带有一个形式电荷的卤离子主要是通过色散力——而非静电力——来发挥其稳定化效应。这可解释为尽管卤离子可与周围蛋白质基团发生显著的Coulomb吸引作用,但由此获得的有利静电自由能贡献却因形成卤素模体时所伴随的不利静电去溶剂化惩罚而大打折扣了
(6)二维描绘蛋白质复合物界面非键模体：有鉴于蛋白质／蛋白质相互作用在诸多生理和生化过程中扮演了中心的角色,本文为此专门开发了一种二维分子图形学软件包2D-GraLab,用于示意性描绘已知结构蛋白质复合物界面的多样非键模体。该程序提供了图形界面、控制对话框、三维显示窗口等交互方式以便用户使用,并借助一系列业已得到相关领域广泛认可的计算技术和独立程序进行数据处理以确保输出结果的可靠性,进而将所得信息以二维示意图方式加以直观呈现以供研究者观察和分析目标蛋白复合物界面的各类非键作用模式。
The classic view of the central dogma of biology states that "the coded genetic information hard-wired into DNA is transcribed into individual transportable cassettes, composed of messenger RNA (mRNA); each mRNA cassette contains the program for synthesis of a particular protein sequence." With the progress in the field of biology at subcellular level in recent years, however, our notion about the complete pathway of the genetic information-flow is enlarged to cover biomolecular folding and recognition—that are fundamentally dominated by weak, reversible chemical forces, or called biological noncovalent interactions (BNIs). Here, we further extended the concept of BNI to biological noncovalent motif (BNM) as a description of the functional entity composed of one or several BNIs in biological context. In this dissertation, we define, analyze, and demonstrate a series of specific BNMs that are largely underappreciated in the sophisticated biochemical community. In addition, an in-house program called the 2D-GraLab is also described for automatically generating schematic representation of BNMs across the protein binding interfaces.
(ⅰ) Sulfur-containing hydrogen bonds in proteins. Sulfur atoms have been known to participate in hydrogen bonds (H-bonds) and these sulfur-containing H-bonds (SCHBs) are suggested to play important roles in certain biological processes. This study aims to comprehensively characterize all the SCHBs in 500 high-resolution (<1.8 A) protein structures retrieved from the Top500 database. We categorize SCHBs into six types according to donor/acceptor behaviors and then employ explicit hydrogen approach to distinguish SCHBs from those of non-hydrogen bonding interactions. It is revealed that sulfur atom is a very poor H-bond acceptor, but a moderately good H-bond donor. In a-helix, considerable SCHBs are found between the sulphydryl group of cysteine residueⅰand the carbonyl oxygen of residueⅰ-4, and these SCHBs exert appreciable effect in stabilizing helices. Although for most SCHBs, they possess no specific secondary structure preference, their geometrical characteristics in proteins and in free small compounds are significantly distinct, indicating that protein SCHBs are geometrically distorted. Interestingly, sulfur atom in disulfide bond tends to form bifurcated H-bond whereas in cysteine-cysteine pairs prefer to form dual H-bond. These special H-bonds remarkably boost the interaction between H-bond donor and acceptor. By oxidation/reduction manner, the mutual transformation between the dual H-bonds and disulfide bonds for cysteine-cysteine pairs can accurately adjust the structural stability and biological function of proteins in different environments. Furthermore, few loose H-bonds are observed to form between the sulphydryl groups and aromatic rings, and in these cases the donor H is almost over against the rim rather than the center of the aromatic ring.
(ⅱ) Fluorine bonds at protein-ligand interfaces. Although fluorination of pharmacologically active compounds has long been a common strategy to increase their metabolic stability and membrane permeation, the functionality of protein-ligand interactions involving fluorine atoms, that we named fluorine bonds, was only recently recognized in chemistry and biology communities. Here, the geometrical characteristics and energetic behaviors of fluorine bonds are systematically investigated by combining two quite disparate but complementary approaches:X-ray structural analysis and theoretical calculations. We find that the short contacts involving fluorine atoms between proteins and fluorinated ligands are very frequent and these contacts, compared to those of routine hydrogen/halogen bonds, are more similar to above-mentioned SCHBs. ONIOM-based QM/MM analysis further reveal that fluorine bonds do play an essential role in protein-ligand binding, albeit the strength of isolated fluorine bonding is quite modest. Furthermore, 14 quantum mechanics (QM) and molecular mechanics (MM) methods are performed to reproduce fluorine bond energies obtained at the rigorous MP2/aug-cc-pVDZ level of theory, and results show that most QM methods and very few MM methods perform well in the reproducibility; the MPWLYP functional and MMFF94 force field are recommended to study moderate and large fluorine bonding systems, respectively.
(ⅲ) Halogen-water-hydrogen bridges in biomolecules. The importance of water in biological systems has long been recognized in the field of biology. Here, we describe a new manner by which water affects biomolecular behaviors, called halogen-water-hydrogen bridge (XWH bridge), that is, one H-bond in water-mediated H-bond bridge is replaced functionally by a halogen bond (X-bond). Although behaving similarly to water-mediated H-bond motif, the XWH bridge usually stands in multifurcated forms and possesses stronger directionality. QM analysis on several model and real systems reveals that the XWH bridges are more thermodynamically stable than other water-involved interactions, and this stability is further enhanced by the cooperation between X-bond and H-bond. Crystal structure survey clearly demonstrates the significance of XWH bridges in stabilization of biomolecular conformations and in mediation of protein-protein, protein-nucleic acid, and receptor-ligand recognition and binding.
(ⅳ) Halogen-ionic bridges in biomolecules. If considering that the pronouncedly charged halide anions are ubiquitous in the biological world, then it is interesting to ask whether the halogen-ionic bridges—this term is named by us to describe the interaction motif of a nonbonded halogen ion with two or more electrophiles simultaneously—commonly exist in biomolecules and how they contribute to the stability and specificity of biomolecular folding and binding? To address these problems, we herein present a particularly systematic investigation on the geometrical profile and energy landscape of halogen ions interacting with and bridging between polar and charged molecular moieties in small model systems and real crystal structures, by means of ab initio calculation, database survey, continuum electrostatic analysis, and hybrid QM/MM examination. All of these unequivocally demonstrate that this putative halide motif is broadly distributed in biomolecular systems (>6000) and can confer a substantial stabilization for the architecture of proteins and their complexes with nucleic acids and small ligands. This stabilization energy is estimated to be generally more than 100 kcal·mol-1 for gas-phase state or about 20 kcal·mol-1 for solution condition, which is much greater than that found in sophisticated water-mediated bridge (<10 kcal·mol-1) and salt bridge (～3.66 kcal·mol-1).
(ⅴ) Contribution of halide motifs to protein stability. Halide anions are traditionally recognized as the structure maker and breaker of water to indirectly influence the physicochemical and biological properties of biomacromolecules immersing in electrolyte solution, but here we are more interested in whether they can be structured in protein interior, forming that we named halide motifs, to stabilize the protein architecture through direct noncovalent interactions with their context? In the current work, we present a systematical investigation on the energy components in 782 high-quality protein halide motifs retrieved from the Protein Data Bank (PDB), by means of the continuum electrostatic analysis coupled with non-electrostatic considerations as well as hybrid QM/MM examination. We find that most halide motifs (91.6%) in our dataset are substantially stabilizing and their average stabilization energy is significantly larger than that previously obtained for sophisticated protein salt bridges (-15.16 vs.-3.66 kcal·mol-1). Strikingly, non-electrostatic factors, especially the dispersion potential, rather than the electrostatic aspect, dominate the energetic profile of the pronouncedly charged halide motifs, since the expensive cost for electrostatic desolvation penalty requires to be paid off using the income receiving from the favorable Coulomb interactions during the motif formation. In addition, all the energy terms involved in halide motifs, regardless of their electrostatic or non-electrostatic nature, show to highly depend on the degree of motif's burial in protein, and the buried halide motifs are generally associated with a high stability.
(vi) 2D depiction of interfacial NBMs for protein complexes. A program called the 2D-GraLab is described for automatically generating schematic representation of diverse NBMs across the protein binding interfaces. The input file of this program takes the standard PDB format, and the outputs are two-dimensional PostScript diagrams giving intuitive and informative description of the protein-protein interactions and their energetics properties, including hydrogen bond, salt bridge, van der Waals interaction, hydrophobic contact, p-p stacking, disulfide bond, desolvation effect, and loss of conformational entropy. To ensure the accuracy and reliability of determined interaction information, methods and standalone programs employed in the 2D-GraLab are all widely used in the chemistry and biology communities. The generated diagrams allow intuitive visualization of the interaction mode and binding specificity between two subunits in protein complexes, and by providing information on nonbonding energetics and geometrical characteristics, the program offers the possibility of comparing different protein binding profiles in a detailed, objective, and quantitative manner.
引文
1. Sanger, F. Nobel Lecture:The Chemistry of Insulin; 1958.
2. Perutz, M. F.; Kendrew, J. C. Nobel Lecture:Myoglobin and the Structure of Proteins; 1962.
3. Barabasi, A.-L.; Oltvai, Z. N. Network biology:understanding the cell's functional organization. Nat. Rev.2004,5,101-113.
4. Gomase, V. S.; Changbhale, S. S.; Patil, S. A.; Kale, K. V. Metabolomics. Curr. Drug Metab.2008,9,89-98.
5. Ideker, T.; Galitski, T.; Hood, L. A new approach to decoding life:systems biology. Annu. Rev. Genomics Hum. Genet.2001,2,343-372.
6. Andrianantoandro, E.; Basu, S.; Karig, D. K.; Weiss, R. Synthetic biology:new engineering rules for an emerging discipline. Mol. Syst. Biol.2006,2, 2006.0028.
7. Lawrence, M. C.; Colman, P. M. Shape complementarity at protein/protein interfaces.J. Mol. Biol.1993,234,946-950.
8. Clackson, T.; Wells, J. A. A hot spot of binding energy in a hormone-receptor interface. Science 1995,267,383-386.
9. Wear, M. A.; Kan, D.; Rabu, A.; Walkinshaw, M. D. Experimental determination of van der Waals energies in a biological system. Angew. Chem. Int. Ed.2007,119,6573-6576.
10. Chen, C. M. Lattice model of transmembrane polypeptide folding. Phys. Rev. 2001,63,010901R.
11. Errington, N.; Doig, A. J. A phosphoserine-lysine salt bridge within an a-helical peptide, the strongest a-helix side-chain interaction measured to date. Biochemistry 2005,44,10449-10456.
12. Gervasio, F. L.; Chelli, R.; Procacci, P.; Schettino, V. The nature of intermolecular interactions between aromatic amino acid residues. Proteins 2002,48,117-125.
13. Desiraju, G. R. Hydrogen bridges in crystal engineering:interactions without borders. Ace. Chem. Res.2002,35,565-573.
14. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based recognition processes:a world parallel to hydrogen bonding. Ace. Chem. Res. 2005,38,386-395.
15. Green, D. E.; Zande, H. D. V. Universal energy principle of biological systems and the unity of bioenergetics. Proc. Natl. Acad. Sci. USA 1981,78,5344-5347.
16. Latimer, W. M.; Rodebush, W. H. Polarity and ionization from the standpoint of the Lewis theory of valence. J. Am. Chem. Soc.1920,42,1419-1433.
17. Pauling, L. The Nature of the Chemical Bond; Ithaca:Cornell University Press, 1960.
18. Pauling, L.; Corey, R. B.; Branson, H. R. Two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl Acad. Sci. USA 1951,37, 205-211.
19. Watson J. D.; Crick F. H. C. A structure for deoxyribose nucleic acid. Nature 1953,171,737-738.
20. Fershta A. R. The hydrogen bond in molecular recognition. Trends Biochem. Sci.1987,12,301-304.
21. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based recognition processes:a world parallel to hydrogen bonding. Acc. Chem. Res. 2005,38,386-395.
22. Clark, T.; Hennemann, M.; Murray, J. S.; Politzer, P. Halogen bonding:the s-hole. J. Mol. Model.2007,13,291-296.
23. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl Acad. Sci. USA 2004,101,16789-16794.
24. Voth, A. R.; Hays, F. A.; Ho, P. S. Directing macromolecular conformation through halogen bonds. Proc. Natl Acad. Sci. USA 2007,104,6188-6193.
25. Lu, Y.; Shi, T.; Wang, Y.; Yang, H.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. Halogen bonding—a novel interaction for rational drug design? J. Med. Chem. 2009,52,2854-2862.
26. Jeschke, P. The unique role of halogen substituents in the design of modern agrochemicals. Pest Manag. Sci.2010,66,10-27.
27. Riley, K. E.; Murray, J. S.; Politzer, P.; Concha, M. S.; Hobza, P. Br…O complexes as probes of factors affecting halogen bonding:interactions of bromobenzenes and bromopyrimidines with acetone. J. Chem. Theory Comput. 2009,5,155-163.
28. Voth, A. R.; Khuu, P.; Oishi, K.; Ho, P. S. Halogen bonds as orthogonal molecular interactions to hydrogen bonds. Nat. Chem.2009,1,74-79.
29. Lu, Y.; Wang, Y.; Xu, Z.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. C-X…H contacts in biomolecular systems:how they contribute to protein-ligand binding affinity. J. Phys. Chem. B 2009,113,12615-12621.
30. Lu, Y.; Wang, Y.; Zhu, W. Nonbonding interactions of organic halogens in biological systems:implications for drug discovery and biomolecular design. Phys. Chem. Chem. Phys.2010,12,4543-4551.
31. Zhou, P.; Tian, F.; Zou, J.; Shang, Z. Rediscovery of halogen bonds in protein-ligand complexes. Mini Rev. Med. Chem.2010,10,309-314.
32. Kraut, D. A.; Churchill, M. J.; Dawson, P. E.; Herschlag, D. Evaluating the potential for halogen bonding in the oxyanion hole of ketosteroid isomerase using unnatural amino acid mutagenesis. ACS Chem. Biol.2009,4,269-273.
33. Kumar, S.; Nussinov, R. Close-range electrostatic interactions in proteins. ChemBioChem 2002,3,604-617.
34. Marqusee, S.; Sauer, R. T. Contribution of a hydrogen bond/salt bridge network to the stability of secondary and tertiary structures in lambda repressor. Protein Sci.1994,3,2217-2225.
35. Pervushin, K.; Billeter, M.; Siegal, G.; Wuthrich, K. Structural role of a buried salt bridge in the 434 repressor DNA-binding domain. J. Mol. Biol.1996,264, 1002-1012.
36. Lounnas, V.; Wade, R. C. Exceptionally stable salt bridges in cytochrome P450cam have functional roles. Biochemistry 1997,36,5402-5417.
37. Singh, U. C. Probing the salt bridge in the dihydrofolate reductase-methotrexate complex by using the coordinate-coupled free energy perturbation method. Proc. Natl. Acad. Sci. USA 1988,85,4280-4284.
38. Barril, X.; Aleman, C.; Orozco, M.; Luque, F. J. Salt bridge interactions: stability of ionic and neutral complexes in the gas phase, in solution and in proteins. Proteins 1998,32,67-79.
39. Sun, D. P.; Sauer, U.; Nicholson, H.; Matthews, B. W. Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. Biochemistry 1991,30,7142-7153.
40. Waldburger, C. D.; Schildbach, J. F.; Sauer, R. T. Are buried salt bridges important for protein stability and conformational specificity? Nat. Struct. Biol. 1995,2,122-128.
41. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol.1999,293,1241-1255.
42. Delcourt, S. G.; Blake, R. D. Stacking energies in DNA. J. Biol. Chem.1991, 266,15160-15169.
43. Cheng, Y. K.; Pettitt, B. M. Stabilities of double- and triple-strand helical nucleic acids. Prog. Biophys. Mol. Biol.1992,58,225-257.
44. Sponer, J.; Gabb, H. A.; Leszczynski, J.; Hobza, P. Base-base and deoxyribose-base stacking interactions in B-DNA and Z-DNA:a quantum-chemical study. Biophys. J.1997,73,76-87.
45. Ryeha, D.; Kabelac, M.; Ryjacek, F.; Syponer, J.; Syponer, J. E.; Elstner, M.; Suhai, S.; Hobza, P. Intercalators.1. Nature of stacking interactions between intercalators (ethidium, daunomycin, ellipticine, and 4',6-diaminide-2-phenylindole) and DNA base pairs. Ab initio quantum chemical, density functional theory, and empirical potential study. J. Am. Chem. Soc 2002,124,3366-3376.
46. Manalo, M. N.; Perez, L. M.; Wang, A. L. Hydrogen-bonding and p-p base-stacking interactions are coupled in DNA, as suggested by calculated and experimental trans-H-bond deuterium isotope shifts. J. Am. Chem. Soc.2007, 129,11298-11299.
47. Li, S.; Cooper, V. R.; Thonhauser, T.; Lundqvist, B. I.; Langreth, D. C. Stacking interactions and DNA intercalation. J. Phys. Chem. B 2009,113, 11166-11172.
48. McGaughey, G. B.; Gagne, M.; Rappe, A. K. p-stacking interactions. Alive and well in proteins. J. Biol. Chem.1998,273,15458-15463.
49. Gervasio, F. L.; Chelli, R.; Procacci, P.; Schettino, V. The nature of intermolecular interactions between aromatic amino acid residues. Proteins 2002,48,117-125.
50. Chelli, R.; Gervasio, F. L.; Procacci, P.; Schettino, V. Stacking and T-shape competition in aromatic-aromatic amino acid interactions. J. Am. Chem. Soc., 2002,124,6133-6143.
51. Rutledge, L. R.; Wetmore, S. D. Remarkably strong T-shaped interactions between aromatic amino acids and adenine:their increase upon nucleobase methylation and a comparison to stacking. J. Chem. Theory Comput.2008,4, 1768-1780.
52. Dougherty, D. A. Cation-p interactions in chemistry and biology:a new view of benzene, Phe, Tyr, and Trp. Science 1996,271,163-168.
53. Gallivan, J. P.; Dougherty, D. A. Cation-p interactions in structural biology. Proc. Natl Acad. Sci. USA 1999,96,9459-9464.
54. Crowley, P. B.; Golovin, A. Cation-p interactions in protein-protein interfaces. Proteins 2005,59,231-239.
55. Wintjens, R.; Lievin, J.; Rooman, M.; Buisine, E. Contribution of cation-p interactions to the stability of protein-DNA complexes. J. Mol. Biol.2000,302, 393-408.
56. Scharer, K.; Morgenthaler, M.; Paulini, R.; Obst-Sander, U.; Banner, D. W.; Schlatter, D.; Benz, J.; Stihle, M.; Diederich, F. Quantification of cation-p interactions in protein-ligand complexes:crystal structure analysis of factor Xa bound to a quaternary ammonium ion ligand. Angew. Chem. Int. Ed.2005,44, 4400-4404.
57. Garde, S.; Hummer, G.; Garcia, A. E.; Paulaitis, M. E.; Pratt, L. R. Origin of entropy convergence in hydrophobic hydration and protein folding. Phys. Rev. Lett.1996,77,4966-4968.
58. Jungwirth, P.; Zahradnik, R. The entropy driven hydrophobic effect as a function of solute—solvent interactions. A molecular dynamics study. Chem. Phys. Lett.1994,217,319-324.
59. Tsai, C. J.; Lin, S. L.; Wolfson, H. J.; Nussino, R. Studies of protein-protein interfaces:a statistical analysis of the hydrophobic effect. Protein Sci.1997,6, 53-64.
60. Akahane, K.; Nagano, Y.; Umeyama, H. Hydrophobic effect on the protein-ligand interaction; hydrophobic field-effect index and hydrophobic correlation index. Chem. Pharm. Bull.1989,37,86-92.
61. Spyrakis, F.; Cozzini, P.; Bertoli, C.; Marabotti, A.; Kellogg, G. E.; Mozzarelli, A. Energetics of the protein-DNA-water interaction. BMC Struct. Biol.2007,7, 4.
62. Buckingham, A. D.; Fowler, P. W.; Hutson, J. M. Theoretical studies of van der Waals molecules and intermolecular forces. Chem. Rev.1988,88,963-988.
63. Roth, C. M.; Neal, B. L.; Lenhoff, A. M. van der Waals interactions involving proteins. Biophys. J.1996,70,977-987.
64. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz Jr, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules.J. Am. Chem. Soc.1995,117,5179-5197.
65. Ott, K.-H.; Meyer, B. Parametrization of GROMOS force field for oligosaccharides and assessment of efficiency of molecular dynamics simulations.J. Comput. Chem.1996,17,1068-1084.
66. Morris, G. M.; Goodsell, D. S. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998,19,1639-1662.
67. Verdonk, M. L.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Taylor, R. D. Improved protein-ligand docking using GOLD. Proteins 2003,52,609-623.
68. Honig, B.; Nicholls, A. Classical electrostatics in biology and chemistry. Science 1995,268,1144-1149.
69. Fogolari, F.; Brigo, A.; Molinari, H. The Poisson-Boltzmann equation for biomolecular electrostatics:a tool for structural biology. J. Mol. Recognit.2002, 15,377-392.
70. Rocchia, W.; Alexov, E.; Honig, B. Extending the applicability of the nonlinear Poisson-Boltzmann equation:multiple dielectric constants and multivalent ions. J. Phys. Chem. B 2001,105,6507-6514.
71. McCoy, A. J.; Chandana, V.; Colman, P. M. Electrostatic complementarity at protein/protein interfaces.J. Mol. Biol.1997,268,570-584.
72. Ledvina, P. S.; Yao, N.; Choudhary, A.; Quiocho, F. A. Negative electrostatic surface potential of protein sites specific for anionic ligands. Proc. Natl. Acad. Sci. USA 1996,93,6786-6791.
73. Norberg, J. Association of protein-DNA recognition complexes:electrostatic and nonelectrostatic effects. Arch. Biochem. Biophys.2003,410,48-68.
74. D'Aquino, J.A.; Gomez, J.; Hilser, V. J.; Lee, K. H.; Amzel, L. M.; Fieire, E. The magnitude of the backbone conformational entropy change in protein folding. Proteins 1996,25,143-156.
75. Koehl, P.; Delarue, M. Application of a self-consistent mean field theory to predict protein side-chains conformation and estimate their conformational entropy. J. Mol. Biol.1994,239,249-275.
76. Zhang, J.; Liu, J. S. On side-chain conformational entropy of proteins. PLoS Comput. Biol.2006,2, e168.
77. Karplus, M.; Lchiye, T.; Pettitt, B. M. Configurational entropy of native proteins. Biophys. J.1987,52,1083-1085.
78. Doig, A. J.; Sternberg, M. J. E. Side-chain conformational entropy in protein folding. Protein Sci.1995,4,2247-2251.
79. Fischer, S.; Verma, C. S. Binding of buried structural water increases the flexibility of proteins. Proc. Natl. Acad. Sci. USA 1999,96,9613-9615.
80. Fischer, S.; Smith, J. C.; Verma, C. S. Dissecting the vibrational entropy change on protein/ligand binding:burial of a water molecule in bovine pancreatic trypsin inhibitor. J. Phys. Chem. B 2001,105,8050-8055.
81. McMahon, T. B.; Kebarle, P. Strong hydrogen bonding in gas-phase ions:a high-pressure mass-spectrometric study of formation and energetics of methyl fluoride proton-bound dimmer. J. Am. Chem. Soc.1986,108,6502-6505.
82. Legon, A. C.; Millen, D. A. Directional character, strength,. and nature of the hydrogen bond in gas-phase dimmers. Acc. Chem. Res.1987,20,39-46.
83. Iqbal, M.; Balaram, P. The 310 helical conformation of the amino terminal decapeptide of suzukacillin.270 MHz hydrogen-1 NMR evidence for eight intramolecular hydrogen bonds. J. Am. Chem. Soc.1981,103,5548-5552.
84. Menard, R.; Plouffe, C.; Khouri, H. E.; Dupras, R.; Tessier, D. C; Vernet, T. Thomas, D. Y.; Storer, A. C. Removal of an inter-domain hydrogen bond through site-directed mutagenesis:role of serine 176 in the mechanism of papain. Protein Eng.1991,4,307-311.
85. Sun, D. P.; Sauer, U.; Nicholson, H.; Matthews, B. W. Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. Biochemistry 1991,30,7142-7153.
86. Barratt, E.; Bingham, R. J.; Warner, D. J.; Laughton, C. A.; Phillips, S. E. V.; Homans, S. W. van der Waals interactions dominate ligand-protein association in a protein binding site occluded from solvent water. J. Am. Chem. Soc.2005, 127,11827-11834.
87. Ramanadham, M.; Jakkal, V. S.; Chidambaram, R. Carboxyl group hydrogen bonding in X-ray protein structures analysed using neutron studies on amino acids. FEBS Lett.1993,323,203-206.
88. Chatake, T.; Higuchi, Y.; Mizuno, N.; Tanak, I.; Niimura, N.; Morimotoa, Y. Hydrogen bonds of DsrD protein revealed by neutron crystallography. J. Synchrotron Radiat. 2008,15,277-280.
89. Alexandrescu, A. T.; Snyder, D. R.; Abildgaard, F. NMR of hydrogen bonding in cold-shock protein A and an analysis of the influence of crystallographic resolution on comparisons of hydrogen bond lengths. Protein Sci.2001,10, 1856-1868.
90. Bartlett, R. J.; Schweigert, I. V.; Lotrich, V. F. Ab initio DFT:getting the right answer for the right reason. J. Mol. Struct. (Theochem) 2006,771,1-8.
91.林梦海.量子化学计算方法与应用；科学出版社：北京,2004.
92. Lill, S. O. N. Application of dispersion-corrected density functional theory. J. Phys. Chem. A 2009,113,10321-10326.
93. Foster, J. P.; Weinhold, F. Natural atomic orbitals and natural population analysis. J. Am. Chem. Soc.1980,102,7211-7218.
94. Bader, R. F. W. Atoms in Molecules:A Quantum Theory; Oxford University Press:UK,1990.
95. Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J. Chem. Theory Comput.2006,2, 815-826.
96. Senthilkumar, K.; Mujika, J. I.; Ranaghan, K. E.; Manby, F. R.; Mulholland, A. J.; Harvey, J. N. Analysis of polarization in QM/MM modelling of biologically relevant hydrogen bonds. J. R. Soc. Interface 2008,5,207-216.
97. Lu, S.-Y.; Jiang, Y.-J.; Zhou, P.; Zou, J.-W.; Wu, T.-X. Geometric characteristics and energy landscapes of halogen-water-hydrogen bridges at protein-ligand interfaces. Chem. Phys. Lett.2010,485,348-353.
98. Sundaresan, N.; Pillai, C. K. S.; Suresh, C. H. Role of Mg2+ and Ca2+ in DNA bending:evidence from an ONIOM-based QM-MM study of a DNA fragment. J. Phys. Chem. A 2006,110,8826-8831.
99. Guallar, V.; Wallrapp, F. Mapping protein electron transfer pathways with QM/MM methods. J. R. Soc. Interface 2008,5, S233-S239.
100. Goedecker, S. Linear scaling electronic structure methods. Rev. Mod. Phys. 1999,71,1085-1123.
101. Cole, D. J.; Skylaris, C.-K.; Rajendra, E.; Venkitaraman, A. R.; Payne M. C. Protein-protein interactions from linear-scaling first-principles quantum-mechanical calculations. Europhys. Lett.2010,91,37004.
102. Muzet, N.; Guillot, B.; Jelsch, C.; Howard, E.; Lecomte, C. Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations. Proc. Natl. Acad. Sci. USA 2003,100,8742-8747.
103. MacKerell Jr, A. D.; Bashford, D.; Bellott, M.; Dunbrack Jr, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy,'D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher Ⅲ, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 1998,102,3586-3616.
104. Jorgensen, W. J.; Maxwell, D. S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc.1996,118,11225-11236.
105. Adcock, S. A.; McCammon, J. A. Molecular dynamics:survey of methods for simulating the activity of proteins. Chem. Rev.2006,106,1589-1615.
106. Kendrew, J. C.; Bodo, G.; Dintzis, H. M.; Parrish, R. G.; Wyckoff, H.; Phillips, D. C. A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 1958,181,662-666.
107. Berman H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
108. Hermans, J. Hydrogen bonds in molecular mechanics force fields. Adv. Protein Chem.2005,72,105-119.
109. Miyazawa, S.; Jernigan, R. L. Estimation of effective interresidue contact energies from protein crystal-structures—quasi-chemical approximation. Macromolecules 1985,18,534-552.
110. Grochowski, P.; Trylska, J. Continuum molecular electrostatics, salt effects, and counterion binding—a review of the Poisson-Boltzmann theory and its modifications. Biopolymers 2008,89,93-113.
111. Jain, A. N. Scoring functions for protein-ligand docking. Curr. Protein Pept. Sci.2006,7,407-420.
112. Zhou, P.; Tian, F.; Lv, F.; Shang, Z. Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins. Proteins 2009,76,151-163.
113. Zhou, P.; Zou, J.; Tian, F.; Shang, Z. Fluorine bonding—how does it work in protein-ligand interactions? J. Chem. Inf. Model.2009,49,2344-2355.
114. Zhou, P.; Lv, J.; Zou, J.; Tian, F.; Shang, Z. Halogen-water-hydrogen bridges in biomolecules. J. Struct. Biol.2010,169,172-182.
115. Zhou, P.; Ren, Y.; Tian, F.; Zou, J.; Shang, Z. Halogen-ionic bridges:do they exist in the biomolecular world? J. Chem. Theory Comput.2010,6,2225-2241.
116. Zhou, P.; Tian, F.; Zou, J.; Ren, Y.; Liu, X.; Shang, Z. Do halide motifs stabilize protein architecture? J. Phys. Chem. B 2010,114,15673-15686.
117. Zhou, P.; Tian, F.; Shang, Z.2D depiction of nonbonding interactions for protein complexes. J. Comput. Chem.2009,30,940-951.
118. Richardson, D. C. The Top500 Database; Kinemages Lab, Duke University:NC, USA.
119. Iwaoka, M.; Komatsu, H.; Katsuda, T.; Tomoda, S. Quantitative evaluation of weak nonbonded Se…F interactions and their remarkable nature as orbital interactions. J. Am. Chem. Soc.2002,124,1902-1909.
120. Matta, C. F.; Castillo, N.; Boyd, R. J. Characterization of a closedshell fluorine-fluorine bonding interaction in aromatic compounds on the basis of the electron density. J. Phys. Chem. A 2005,109,3669-3681.
121. Olsen, J. A.; Banner, D. W.; Seiler, P.; Sander, U. O.; D'Arcy, A.; Stihle, M.; Muller, K.; Diederich, F. A fluorine scan of thrombin inhibitors to map the fluorophilicity/fluorophobicity of an enzyme active site:evidence for C-F…C=O interactions. Angew. Chem., Int. Ed.2003,42,2507-2511.
122. Plenio, H. The Coordination chemistry of fluorine in fluorocarbons. ChemBioChem 2004,5,650-655.
123. Carosati, E.; Sciabola, S.; Crucia, G. Hydrogen bonding interactions of covalently bonded fluorine atoms:from crystallographic data to a new angular function in the GRID force field. J. Med Chem.2004,47,5114-5125.
124. Lu, Y.; Zou, J.; Yu, Q.; Jiang, Y.; Zhao, W. Ab initio investigation of halogen bonding interactions involving fluorine as an electron acceptor. Chem. Phys. Lett.2007,449,6-10.
125. Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals:looking beyond intuition. Science 2007,317,1881-1886.
126. Jeschke, P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem 2004,5,570-589.
127. Meyer, E. Internal water molecules and H-bonding in biological macromolecules:a review of structural features with functional implications. Protein Sci.1992,1,1543-1562.
128. Harding, M. M. The architecture of metal coordination groups in proteins. Acta Cryst.2004, D60,849-859.
129. Zhou, P.; Shang, Z.2D molecular graphics:a flattened world of chemistry and biology. Brief. Bioinform.2009,10,247-258.
1. Zhou, P.; Tian, F.; Lv, F.; Shang, Z. Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins. Proteins 2009,76,151-163.
2. Jeffrey, G. A.; Saenger, W. Hydrogen Bonding in Biological Structures; Springer-Verlag:Berlin,1991.
3. Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond in Structural Chemistry and Biology; Oxford University Press:New York,1999.
4. Jiang, L.; Lai, L. C-H…O hydrogen bonds at protein-protein interfaces. J. Biol. Chem.2002,277,37732-37740.
5. Carosati, E.; Sciabola, S.; Cruciani, G. Hydrogen bonding interactions of covalently bonded fluorine atoms:from crystallographic data to a new angular function in the GRID force field. J. Med. Chem.2004,47,5114-5125.
6. Brandl, M.; Weiss, M. S.; Jabs, A.; Suhnel, J.; Hilgenfeld, R. C-H…p interactions in proteins. J. Mol. Biol.2001,307,357-377.
7. Scheiner, S. Hydrogen Bonding. A Theoretical Perspective; Oxford University Press:New York,1997.
8. Gilli, G.; Gilli, P. Towards an unified hydrogen-bond theory. J. Mol. Struct. 2000,552,1-15.
9. Pimentel, G. C.; Mcclellan, A. L. The Hydrogen Bond; Freeman:San Franciso, 1960.
10. Sabin, J. R. Hydrogen bonds involving sulfur. Ⅰ. The hydrogen sulfide dimer. J. Am. Chem. Soc.1971,93,3613-3620.
11. Sabin, J. R. Hydrogen bonds involving sulfur. Ⅱ. The hydrogen sulfide-hydrosulfide complex. J. Chem. Phys.1971,54,4675-4680.
12. Platts, J. A.; Howard, S. T.; Bracke, B. R. F. Directionality of hydrogen bonds to sulfur and oxygen. J. Am. Chem. Soc.1996,118,2726-2733.
13. Wennmohs, F.; Staemmler, V.; Schindler, M. Theoretical investigation of weak hydrogen bonds to sulfur. J. Chem. Phys.2003,119,3208-3218.
14. Allen, F. H.; Bird, C. M.; Rowland, R. S.; Raithby, P. R. Hydrogen-bond acceptor and donor properties of divalent sulfur (Y-S-Z and R-S-H). Acta Cryst.1997,B53,696-701.
15. Steiner, T. S-H…S hydrogen-bond chain in thiosalicylic acid. Acta Cryst.2000, C56,876-877.
16. Krepps, M. K.; Parkin, S.; Atwood, D. A. Hydrogen bonding with sulfur. Cryst. Growth Des.2001,1,291-297.
17. Tsunehiko, H.; Noriyuki, S.; Tetsuo, N. Effect of hydrogen bond toward the sulfur atom on electron transfer activity of metal-sulfur complexes. Sanka Hanno Toronkai Koen Yoshishu 2001,34,97-99.
18. Kamphuis, I. G.; Drenth, J.; Baker, E. N. Thiol proteases. Comparative studies based on the high-resolution structures of papain and actinidin, and on amino acid sequence information for cathepsins B and H, and stem bromelain. J. Mol. Biol.1985,182,317-329.
19. Bazan, J. F.; Fletterick, R. J. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases:structural and functional implications. Proc. Natl. Acad. Sci. USA 1988,85,7872-7876.
20. Beck, B. W.; Xie, Q.; Ichiye, T. Sequence determination of reduction potentials by cysteinyl hydrogen bonds and peptide dipoles in [4Fe-4S] ferredoxins. Biophys. J.2001,81,601-613.
21. Gregoret, L. M.; Rader, S. D.; Fletterick, R. J.; Cohen, F. E. Hydrogen bonds involving sulfur atoms in proteins. Proteins 1991,9,99-107.
22. Rajagopal, S.; Vishveshwara, S. Short hydrogen bonds in proteins. FEBS J. 2005,272,1819-1832.
23. Panigrahi, S. K.; Desiraju, G. R. Strong and weak hydrogen bonds in the protein-ligand interface. Proteins 2007,67,128-141.
24. Pal, D.; Chakrabarti, P. Non-hydrogen bond interactions involving the methionine sulfur atom. J. Biomol. Struct. Dyn.2001,19,115-128.
25. Richardson, D. C. The Top500 Database; Kinemages Lab, Duke University:NC, USA.
26. Word, J. M.; Lovell, S. C.; LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol.1999,285,1711-1733.
27. Engh, R. A.; Huber, R. Accurate bond and angle parameters for X-ray protein structure refinement. Acta Cryst.1991, A47,392-400.
28. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
29. Brunger, A. T.; Karplus, M. Polar hydrogen positions in proteins:empirical energy placement and neutron diffraction comparison. Proteins 1988,4, 148-156.
30. Forrest, L. R.; Honig, B. An assessment of the accuracy of methods for predicting hydrogen positions in protein structures. Proteins 2005,61,296-309.
31. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins. J. Mol. Biol.1994,238,777-793.
32. Steiner, T.; Koellner, G. Hydrogen bonds with p-acceptors in proteins: frequencies and role in stabilizing local 3D structures. J. Mol. Biol.2001,305, 535-557.
33. Viswanathan, R.; Dyke, T. R. The structure of H2S…HF and the stereochemistry of the hydrogen bond. J. Chem.Phys.1982,77,1166-1174.
34. Willoughby, L. C.; Fillery-Travis, A. J.; Legon, A. C. An investigation of the rotational spectrum of H2S…HF by pulsed-nozzle, Fourier-transform microwave spectroscopy:determination of the hyperfine coupling constants χaa(33S), χaaD, and DaaH(D)F. J. Chem. Phys.1984,81,20-26.
35. Legon, A. C.; Millen, D. A. Directional character, strength, and nature of the hydrogen bond in gas-phase dimers. Acc. Chem. Res.1987,20,39-46.
36. Gray, T. M.; Matthews, B. W. Intrahelical hydrogen bonding of serine, threonine, and cysteine residues within a-helices and its relevance to membrane-bound proteins. J. Mol. Biol.1984,175,75-81.
37. Thornton, J. M. Disulphide bridges in globular proteins. J. Mol. Biol.1981,151, 261-287.
1. Zhou, P.; Zou, J.; Tian, F.; Shang, Z. Fluorine bonding—how does it work in protein-ligand interactions? J. Chem. Inf. Model.2009,49,2344-2355.
2. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based on recognition processes:a world parallel to hydrogen bonding. Acc. Chem. Res. 2005,38,386-395.
3. Dunitz, J. D.; Taylor, R. Organic fluorine hardly ever accepts hydrogen bonds. Chem. Eur. J.1997,3,89-98.
4. Alkortaa, I.; Rozasa, I.; Elgueroa, J.; Foces-Foces, C.; Canob, F. H. A statistical survey of the Cambridge structural database concerning density and packing. J. Mol. Struct.1996,382,205-213.
5. Ahuja, R.; Samuelson, A. G. Nonbonding interactions of anions with nitrogen heterocycles and phenyl rings:a critical Cambridge structural database analysis. CrystEngComm 2003,5,395-399.
6. Awwadi, F. F.; Willett, R. D.; Peterson, K. A.; Twamley, B. The nature of halogen…halogen synthons:crystallographic and theoretical studies. Chem. Eur. J.2006,12,8952-8960.
7. Kawahara, S.; Tsuzuki, S.; Uchimaru, T. Theoretical study of the C-F/p interaction:attractive tnteraction between fluorinated alkane and an electron-deficient p-system. J. Phys. Chem. A 2004,108,6744-6749.
8. Riley, K. E.; Merz, K. M. Effects of fluorine substitution on the edge-to-face interaction of the benzene dimer. J. Phys. Chem. B 2005,109, 17752-17756.
9. Chopra, D.; Nagarajan, K.; Row, T. N. G. Analysis of weak interactions involving organic fluorine:insights from packing features in substituted 4-keto-tetrahydroindoles. J. Mol. Struct.2008,888:70-83.
10. Vishnumurthy, K.; Row, T. N.; Venkatesan, K. Fluorine in crystal engineering: photodimerization of (1E,3E)-1-phenyl-4-pentafluorophenylbuta-1,3-dienes in the crystalline state. Photochem. Photobiol. Sci.2002,1,427-430.
11. Jackel, C.; Koksch, B. Fluorine in peptide design and protein engineering. Eur. J. Org. Chem.2005,21,4483-4503.
12. Borisenko, K. B.; Broschag, M.; Hargittai, I.; Klapo"tke, T. M.; Schroder, D.; Schulz, A.; Schwarz, H.; Tornieporth-Oetting, I. C.; White, P. S. Preparation of N(SeCl)2+X-(X=SbCl6 or FeCl4), F3CCSeNSeCCF3+SbCl6-, F3CCSeNSeCCF3, F3CCSeNSeCCF3 and F3CCSeSeC(CF3)C(CF3)SeSeCCF3. Electron diffraction study of F3CCSeSeCCF3 and crystal structure of the eight-membered heterocycle F3CCSeSeC(CF3)C(CF3)SeSeCCF3. J. Chem. Soc., Dalton Trans. 1994,2705-2712.
13. Iwaoka, M.; Komatsu, H.; Katsuda, T.; Tomoda, S. Quantitative evaluation of weak nonbonded Se…F interactions and their remarkable nature as orbital interactions. J. Am. Chem. Soc.2002,124,1902-1909.
14. Matta, C. F.; Castillo, N.; Boyd, R. J. Characterization of a closed-shell fluorine-fluorine bonding interaction in aromatic compounds on the basis of the electron density. J. Phys. Chem. A 2005,109,3669-3681.
15. Lee, S.; Mallik, A. B.; Fredrickson, D. C. Dipolar-dipolar interactions and the crystal packing of nitriles, ketones, aldehdyes, and C(sp2)-F groups. Cryst. Growth Des.2004,4,279-290.
16. Olsen, J. A.; Banner, D. W.; Seiler, P.; Sander, U. O.; D'Arcy, A.; Stihle, M.; Muller, K.; Diederich, F. A fluorine scan of thrombin inhibitors to map the fluorophilicity/fluorophobicity of an enzyme active site:evidence for C-F-C=O interactions. Angew. Chem. Int. Ed.2003,42,2507-2511.
17. Plenio, H. The Coordination chemistry of fluorine in fluorocarbons. ChemBioChem 2004,5,650-655.
18. Lu, Y.; Zou, J.; Yu, Q.; Jiang, Y.; Zhao, W. Ab initio investigation of halogen bonding interactions involving fluorine as an electron acceptor. Chem. Phys. Lett.2007,449,6-10.
19. Kovacs, A.; Varga, Z. Halogen acceptors in hydrogen bonding. Coord. Chem. Rev.2006,250,710-727.
20. Bettinger, H. F. How good is fluorine as a hydrogen-bond acceptor in fluorinated single-walled carbon nanotubes? ChemPhysChem 2005,6, 1169-1174.
21. Parsch, J.; Engels, J. W. C-F…H-C hydrogen bonds in ribonucleic acids. J. Am. Chem. Soc.2002,124,5664-5672.
22. Carosati, E.; Sciabola, S.; Crucia, G. Hydrogen bonding interactions of covalently bonded fluorine atoms:from crystallographic data to a new angular function in the GRID force field. J. Med. Chem.2004,47,5114-5125.
23. Bohm, H.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Muller, Obst-Sander, U.; Stahl, M. Fluorine in medicinal chemistry. ChemBioChem 2004,5,637-643.
24. Gerebtzoff, G.; Li-Blatter, X.; Fischer, H.; Frentzel, A.; Seelig, A. Halogenation of drugs enhances membrane binding and permeation. ChemBioChem 2004,5, 676-684.
25. Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals:looking beyond intuition. Science 2007,317,1881-1886.
26. Jeschke, P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem 2004,5,570-589.
27. Paulini, R.; Muller, K.; Diederich, F. Orthogonal multipolar interactions in structural chemistry and biology. Angew. Chem. Int. Ed.2005,44,1788-1805.
28. Kim, C.; Chandra, P. P.; Jain, A.; Christianson, D. W. Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase Ⅱ. J. Am. Chem. Soc.2001,123, 9620-9627.
29. Shin, J.; Cho, D. PDB-Ligand:a ligand database based on PDB for the automated and customized classification of ligand-binding structures. Nucleic Acids Res.2005,33, D238-D241.
30. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
31. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl. Acad. Sci. USA 2004,101,16789-16794.
32. Krivov, G. G.; Shapovalov, M. V.; Dunbrack Jr, R. L. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 2009,77,778-795.
33. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
34. Bondi, A. van der Waals volumes and radii. J. Phys. Chem.1964,68,441-451.
35. Moller, C.; Plesset, M. S. Note on an approximation treatment for many-electron systems. Phys. Rev.1934,46,618-622.
36. Dunning Jr, T. H. The atoms boron through neon and hydrogen. J. Chem. Phys. 1989,90,1007-1023.
37. Sahu, P. K.; Lee, S. Hydrogen-bond interactions in THF-H2O-HF:a theoretical study. Int. J. Quantum. Chem.2007,107,2015-2023.
38. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor. Chim. Acta.1969,13,230-248.
39. Boys, S.F.; Bernardi,F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
40. Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM.J. Chem. Theory Comput.2006,2, 815-826.
41. Adamo, C.; Barone, V. Exchange functionals with improved longrange behavior and adiabatic connection methods without adjustable parameters:the mPW and mPWIPW models. J. Chem. Phys.1998,108,664-675.
42. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, Jr., K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc.1995,117,5179-5197.
43. Lu,Y.;Shi,T.;Wang,Y.;Yang H.;Yan,X.;Luo,X.;Jiang,H.;Zhu,W. Halogen bonding--a novel interaction for rational drug design?J.Med.Chem. 2009,52,2854-2862.
44. Jorgensen,W.L.；Chandrasekhar,J.;Madura,J.D.Impey,R.W.;Klein, M.L.； Comparison of simple potential functions for simulating liquid water,J.Chem. Phys.1983,79,926-935.
45. Comell,W.D.;Cieplak,P.;Bayly,C.I.;Kollman,P.A.Application of RESP charges to calculate conformational energies,hydrogen bond energies,and free energies of solvation.J.Am.Chem.Soc.1993,115,9620-9631.
46. Wang,J.;Wolf, R.M.;Caldwell,J.W.;Kollman,P.A.;Case,D.A.Developing and testing of a general amber force field.J.Comput.Chem.2004,25, 1157-1174.
47. Alzate-Morales,J.H.;Caballero,J.；Jague,A.V.;Nilo,F.D.G. Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2(CDK2)inhibitors:prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculation.J.Chem.Inf. Mode.2009,49,886-899.
48. Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G. E.;Robb,M.A.; Cheeseman,J.R.;Zakrzewski,V G.;Montgomery,J.A.;Stratmann,R.E.; Burant,J.C.;Dapprich,S.;Millam,J.M.;Daniels,A.D.;Kudin,K.N.;Strain, M.C.;Farkas,O.;Tomasi,J.;Barone,V.;Cossi,M.;Cammi,R.；Mennucci,B.； Pomelli,C.;Adamo,C.;Clifford,S.;Ochterski,J.;Petersson,G. A.;Ayala,P.Y.; Cui,Q.；Morokuma,K.；Malick,D.K.;Rabuck,A.D.；Raghavachari,K. Foresman,J.B.;Cioslowski,J.;Ortiz,J.V.;Stefanov,B.B.;Liu,G.;Liashenko, A.；Piskorz,P.;Komaromi,I.;Gomperts,R.;Martin,R.L.;Fox,D.J.;Keith,T.; Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Gonzalez,C.;Challacombe, M.；Gill,P.M.W.;Johnson,B.G.;Chen,W.;Wong,M.W.;Andres,J.L. Head-Gordon,M.;Replogle,E.S.；Pople,J.A.Gaussian 03；Gaussian,Inc., Wallingford,CT,USA,2003.
49. Ponder, J. W.; Richards, F. M. An efficient newton-like method for molecular mechanics energy minimization of large molecules. J. Comput. Chem.1987,8, 1016-1024.
50. HyperChem, version 8.0; Hypercube Inc., Gainesville, FL, USA,2009.
51. Discovery Studio, version 2.1; Accelrys Inc., San Diego, CA, USA,2008.
52. Olsen, J. A.; Banner, D. W.; Seiler, P.; Wagner, B.; Tschopp, T.; Obst-Sander, U.; Kansy, M.; Muller, K.; Diederich, F. Fluorine interactions at the thrombin active site:protein backbone fragments H-Ca-C=O comprise a favorable C-F environment and Interactions of C-F with electrophiles. ChemBioChem 2004,5, 666-675.
53. Fields, B. A.; Bartsch, H. H.; Bartunik, H. D.; Cordes, F.; Guss, J. M.; Freeman, H. C. Accuracy and precision in protein crystal structure analysis:two independent refinements of the structure of poplar plastocyanin at 173 K. Acta Cryst.1994, D50,709-730.
54. Morozov, A. V.; Kortemme, T.; Tsemekhman, K.; Baker, D. Close agreement between the orientation dependence of hydrogen bonds observed in protein structures and quantum mechanical calculations. Proc. Natl. Acad. Sci. USA 2004,101,6946-6951.
55. DiMagno, S.; Sun, H. The strength of weak interactions:aromatic fluorine in drug design. Curr Top. Med. Chem.2006,6,1473-1482.
56. Feyereisen, M. W.; Feller, D.; Dixon, D. A. Hydrogen bond energy of the water dimer. J. Phys. Chem.1996,100,2993-2997.
57. Taylor, R.; Kennard, O.; Versichel, W. Geometry of the N-H…O=C hydrogen bond.1. Lone-pair directionality. J. Am. Chem. Soc.1983,105,5761-5766.
58. Isaacs, E. D.; Shukla, A.; Platzman, P. M.; Hamann, D. R.; Barbiellini, B.; Tulk, C. A. Covalency of the hydrogen bond in ice:a direct X-ray measurement. Phys. Rev. Lett.1999,82,600-603.
59. Obst, U.; Gramlich, V.; Diederich, F.; Weber, L.; Banner, D. W. Design of novel, nonpeptidic thrombin inhibitors and structure of a thrombin-inhibitor complex. Angew. Chem. Int. Ed.1995,34,1739-1742.
60. Obst, U.; Banner, D. W.; Weber, L.; Diederich, F. Molecular recognition at the thrombin active site:structure-based design and synthesis of potent and selective thrombin inhibitors and the X-ray crystal structures of two thrombin-inhibitor complexes. Chem. Biol.1997,4,287-295.
61. Hof, F.; Scofield, D. M.; Schweizer, W. B.; Diederich, F. A weak attractive interaction between organic fluorine and an amide group. Angew. Chem. Int. Ed. 2004,43,5056-5059.
62. Foster, J. P.; Weinhold, F. Natural atomic orbitals and natural population analysis. J. Am. Chem. Soc.1980,102,7211-7218.
63. Lu, Y.; Zou, J.; Fan, J.; Zhao, W.; Jiang, Y.; Yu, Q. Ab initio calculations on halogen-bonded complexes and comparison with density functional methods.J. Comput. Chem.2009,30,725-732.
64. Peterson, S. A.; Klabunde, T.; Lashuel, H. A.; Purkey, H.; Sacchettini, J. C.; Kelly, J. W. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc. Natl. Acad. Sci. USA 1998,95,12956-12960.
65. Kim, C.; Chang, J. S.; Doyon, J. B.; Baird, T. T.; Fierke, C. A.; Jain, A.; Christianson, D. W. Contribution of fluorine to protein-ligand affinity in the binding of fluoroaromatic inhibitors to carbonic anhydrase Ⅱ. J. Am. Chem. Soc. 2000,122,12125-12134.
66. Sorme, P.; Arnoux, P.; Kahl-Knutsson, B.; Leffler, H.; Rini, J. M.; Nilsson, U. J. Structural and thermodynamic studies on cation-p interactions in lectin-ligand complexes:high-affinity galectin-3 inhibitors through fine-tuning of an arginine-arene interaction. J. Am. Chem. Soc.2005,127,1737-1743.
67. Benson, M. L.; Smith, R. D.; Khazanov, N. A.; Dimcheff, B.; Beaver, J.; Dresslar, P.; Nerothin, J.; Carlson, H. A. Binding MOAD, a high-quality protein-ligand database. Nucleic Acids Res.2008,36, D674-D678.
1. Zhou, P.; Lv, J.; Zou, J.; Tian, F.; Shang, Z. Halogen-water-hydrogen bridges in biomolecules. J. Struct. Biol.2010,169,172-182.
2. Levy, Y.; Onuchic, J. N. Water and proteins:a love-hate relationship. Proc. Natl. Acad. Sci. USA 2004,101,3325-3326.
3. Williams, M. A.; Goodfellow, J. M.; Thornton, J. M. Buried waters and internal cavities in monomeric proteins. Protein Sci.1994,3,1224-1235.
4. Janin, J. Wet and dry interfaces:the role of solvent in protein-protein and protein-DNA recognition. Struct. Fold. Des.1999,7, R277-279.
5. Covell, D. G.; Wallqvist, A. Analysis of protein-protein interactions and the effects of amino acid mutations on their energetics. The importance of water molecules in the binding epitope. J. Mol. Biol.1997,269,281-297.
6. Papoian, G. A.; Ulander, J.; Wolynes, P. G. Role of water mediated interactions in protein-protein recognition landscapes. J. Am. Chem. Soc.2003,125, 9170-9178.
7. Lunin, V. V.; Li, Y.; Schrag, J. D.; Iannuzzi, P.; Cygler, M.; Matte, A. Crystal structures of Escherichia coli ATP-dependent glucokinase and its complex with glucose. J. Bacteriol.2004,186,6915-6927.
8. Dreyer, G. B.; Lambert, D. M.; Meek, T. D.; Carr, T. J.; Tomaszek Jr, T. A.; Fernandez, A. V.; Bartus, H.; Cacciavillani, E.; Hassell, A. M. Hydroxyethylene isostere inhibitors of human immunodeficiency virus-1 protease: structure-activity analysis using enzyme kinetics, X-ray crystallography, and infected T-cell assays. Biochemistry 1992,31,6646-6659.
9. Helms, V.; Wade, R. C. Thermodynamics of water mediating protein-ligand interactions in cytochrome P450cam:a molecular dynamics study. Biophys. J. 1995,69,810-824.
10. Jiang, L.; Kuhlman, B.; Kortemme, T.; Baker, D. A "solvated rotamer" approach to modeling water-mediated hydrogen bonds at protein-protein interfaces. Proteins 2005,58,893-904.
11. Bui, H. H.; Schiewe, A. J.; Haworth, I. S. WATGEN:an algorithm for modeling water networks at protein-protein interfaces. J. Comput. Chem.2007,28, 2241-2251.
12. Goodfellow, J. M. Cooperative effects in water-biomolecule crystal systems. Proc. Natl. Acad. Sci. USA 1982,79,4977-4979.
13. Steinbach, P. J.; Brooks, B. R. Protein hydration elucidated by molecular dynamics simulation. Proc. Natl. Acad. Sci. USA 1993,90,9135-9139.
14. Meyer, E. Internal water molecules and hydrogen bonding in biological macromolecules:a review of structural features with functional implications. Protein Sci.1992,1,1543-1562.
15. Sun, Y.; Kollman, P. Are there water bridge-induced hydrophilic interactions. J. Phys. Chem.1996,100,6760-6763.
16. Sevilla, M. D.; Summerfield, S.; Eliezer, I.; Rak, J.; Symons M. C. R. Interaction of the chlorine atom with water:ESR and ab initio MO evidence for three-electron (s2s*1) bonding. J. Phys. Chem. A 1997,101,2910-2915.
17. Davey, J. B.; Legon, A. C. Rotational spectroscopy of the gas phase complex of water and bromine monochloride in the microwave region:geometry, binding strength and charge transfer. Phys. Chem. Chem. Phys.2001,3,3006-3011.
18. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl. Acad. Sci. USA 2004,101,16789-1679.
19. Metrangolo, P.; Resnati, G. Halogen versus hydrogen. Science 2008,321, 918-919.
20. Green, D. E.; Zande, H. D. V. Universal energy principle of biological systems and the unity of bioenergetics. Proc. Natl. Acad. Sci. USA 1981,78,5344-5347.
21. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based recognition processes:a world parallel to hydrogen bonding. Acc. Chem. Res. 2005,38,386-395.
22. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 03; Gaussian, Inc., Wallingford, CT, USA,2003.
23. Legon, A. C.; Thumwood, J. M. A. Properties of the halogen-bonded complex H2S…Br2 established by rotational spectroscopy and ab initio calculations. Phys. Chem. Chem. Phys.2001,3,2758-2764.
24. Legon, A. C.; Thumwood, J. M. A.; Waclawik, E. R. The interaction of water and dibromine in the gas phase:an investigation of the complex H2O…Br2 by rotational spectroscopy and ab initio calculations. Chem. Eur. J.2002,8, 940-950.
25. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor. Chim. Acta.1969,13,230-248.
26. Boys, S. F.; Bernardi, F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
27. Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J. Chem. Theory Comput.2006,2, 815-826.
28. Adamo, C.; Barone, V. Exchange functionals with improved longrange behavior and adiabatic connection methods without adjustable parameters:the mPW and mPWIPW models. J. Chem. Phys.1998,108,664-675.
29. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AM1:a new general-purpose quantum mechanical molecular model. J. Am. Chem. Soc.1985, 107,3902-3909.
30. Lu, Y.; Zou, J.; Fan, J.; Zhao, W.; Jiang, Y.; Yu, Q. Ab initio calculations on halogen-bonded complexes and comparison with density functional methods. J. Comput. Chem.2009,30,725-732.
31. Esseffar, M.; Bouab, W.; Lamsabhi, A.; Abboud, J. L. M.; Notario, R.; Yanez, M. An experimental and theoretical study on some thiocarbonyl-Ⅰ2 molecular complexes. J. Am. Chem. Soc.2000,122,2300-2308.
32. Lu, Y.; Zou, J.; Yu, Q.; Jiang, Y.; Zhao, W. Ab initio investigation of halogen bonding interactions involving fluorine as an electron acceptor. Chem. Phys. Lett.2007,449,6-10.
33. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins. J. Mol Biol.1994,238,777-793.
34. Steiner, T.; Koellner, G. Hydrogen bonds with p-acceptors in proteins: frequencies and role in stabilizing local 3D structures. J. Mol. Biol.2001,305, 535-557.
35. Lu, Y.; Zou, J.; Wang, Y.; Zhang, H.; Yu, Q.; Jiang, Y. A quantitative insight into the'amphiphilicity' of covalently-bonded halogens from ab initio calculations. J. Mol. Struct. (Theochem) 2006,766,119-124.
36. Bondi, A. van der Waals volumes and radii. J. Chem. Phys.1964,68,441-451.
37. Ouvrard, C.; Questel, J. Y. L.; Berthelot, M.; Laurence, C. Halogen-bond geometry:a crystallographic database investigation of dihalogen complexes. Acta. Cryst.2003, B59,512-526.
38. Kortagere, S.; Ekins, S.; Welsh, W. J. Halogenated ligands and their interactions with amino acids:implications for structure-activity and structure-toxicity relationships. J. Mol. Graph. Model.2008,27,170-177.
39. Feyereisen, M. W.; Feller, D.; Dixon, D. A. Hydrogen bond energy of the water dimer. J. Phys. Chem.1996,100,2993-2997.
40. Grabowski, S. J.; Bilewicz, E. Cooperativity halogen bonding effect—ab initio calculations on H2CO…(ClF)n complexes. Chem. Phys. Lett.2006,427,51-55.
41. Li, Q.; Lin, Q.; Li, W.; Cheng, J.; Gong, B.; Sun, J. Cooperativity between the halogen bond and the hydrogen bond in H3N…XY…HF complexes (X, Y=F, Cl, Br). ChemPhysChem 2008,9,2265-2269.
42. Foster, J. P.; Weinhold, F. Natural atomic orbitals and natural population analysis. J. Am. Chem. Soc.1980,102,7211-7218.
43. Rivelino R.; Rivelino R.; Chaudhuri, P.; Canuto, S. Quantifying multiple-body interaction terms in hydrogen-bonded HCN chains with many-body perturbation/coupled-cluster theories. J. Chem. Phys.2003,118,10593-10601.
44. Petukhov, M.; Cregut, D.; Soares, C. M.; Serrano, L. Local water bridges and protein conformational stability. Protein Sci.1999,8,1982-1989.
45. Word, J. M.; Lovell, S. C.; LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol.1999,285,1711-1733.
46. Lommerse, J. P. M.; Stone, A. J.; Taylor, R.; Allen, F. H. The nature and geometry of intermolecular interactions between halogens and oxygen or nitrogen. J. Am. Chem. Soc.1996,118,3108-3116.
47. Mahoney, M. W.; Jorgensen, W. L. A five-site model for liquid water and the reproduction of the density anomaly by rigid, nonpolarizable potential functions. J. Chem. Phys.2000,112,8910-8922.
48. Otting, G.; Liepinsh, E.; Wuthrich, K. Protein hydration in aqueous solution. Science 1991,254,974-980.
49. Ravelli, R. B. G.; Leiros, H. K. S.; Pan, B.; Caffrey, M. McSweeney, S. Specific radiation damage can be used to solve macromolecular crystal structures. Structure 2003,11,217-224.
50. Gerebtzoff, G.; Li-Blatter, X.; Fischer, H.; Frentzel, A.; Seelig, A. Halogenation of drugs enhances membrane binding and permeation. ChemBioChem 2004,5, 676-684.
51. Himmel, D. M.; Das, K.; Clark, A. D.; Hughes, S. H.; Benjahad, A.; Oumouch, S.; Guillemont, J.; Coupa, S.; Poncelet, A.; Csoka, I.; Meyer, C.; Andries, K.; Nguyen, C. H.; Grierson, D. S.; Arnold, E. Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives:a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains. J. Med. Chem.2005,48,7582-7591.
52. Jiang, Y.; Alcaraz, A. A.; Chen, J. M.; Kobayashi, H.; Lu, Y. J.; Snyder, J. P. Diastereomers of dibromo-7-epi-10-deacetylcephalomannine:crowded and cytotoxic taxanes exhibit halogen bonds. J. Med. Chem.2006,49,1891-1899.
53. Voth, A. R.; Ho, P. S. The role of halogen bonding in inhibitor recognition and binding by protein kinases. Curr. Top. Med. Chem.2007,7,1336-1348.
1. Zhou, P.; Ren, Y.; Tian, F.; Zou, J.; Shang, Z. Halogen-ionic bridges:do they exist in the biomolecular world? J. Chem. Theory Comput.2010,6,2225-2241.
2. Hofmeister, F. Zur Lehre von der Wirkung der Salze. Arch. Exp. Pathol. Pharmakol.1888,24,247-260.
3. Marcus, Y. Effect of ions on the structure of water:structure making and breaking. Chem. Rev.2009,109,1346-1370.
4. Zhang, Y.; Cremer, P. S. Interactions between macromolecules and ions:the Hofmeister series. Curr. Opin. Chem. Biol.2006,10,658-663, and references therein.
5. Takashima, K.; Riveros, J. M. Gas-phase solvated negative ions. Mass Spectrom. Rev.1998,17,409-430, and references therein.
6. Kovacs, A.; Varga, Z. Halogen acceptors in hydrogen bonding. Coord. Chem. Rev.2006,250,710-727, and references therein.
7. Arshadi, M.; Yamdagni, R.; Kebarle, P. Hydration of the halide negative ions in the gas phase. Ⅱ. Comparison of hydration energies for the alkali positive and halide negative ions. J. Phys. Chem.1970,74,1475-1482.
8. Caldwell, G.; Kebarle, P. Binding energies and structural effects in halide anion-ROH and-RCOOH complexes from gas-phase equilibria measurements. J. Am. Chem. Soc.1984,106,967-969.
9. Hiraoka, K.; Mizuse, S.; Yamabe, S. Solvation of halide ions with H2O and CH3CN in the gas phase. J. Phys. Chem.1988,92,3943-3957.
10. Bogdanov, B.; Peschke, M.; Tonner, D. S.; Szulejko, J. E.; McMahon, T. B. Stepwise solvation of halides by alcohol molecules in the gas phase. Int. J. Mass Spectrom.1999,187,707-725.
11. Klopper, W.; van Duijneveldt-van de Rijdt, J. G. C. M.; van Duijneveldt, F. B. Computational determination of equilibrium geometry and dissociation energy of the water dimer. Phys. Chem. Chem. Phys.2000,2,2227-2234.
12. Xantheas, S. S.; Dunning Jr, T.H. Structures and energetics of F-(H2O)n, n=1-3, clusters from ab initio calculations. J. Phys. Chem.1994,98,13489-13497.
13. Johnson, M. S.; Kuwata, K. T.; Wong, C. K.; Okumura, M. Vibrational spectrum of I- (H2O). Chem. Phys. Lett.1996,260,551-557.
14. Choi, J. H.; Kuwata, K.T.; Cao, Y. B.; Okumura, M. Vibrational spectroscopy of the Cl-(H2O)n anionic clusters, n=1-5. J. Phys. Chem. A 1998,102,503-507.
15. Kim, J.; Lee, H. M.; Suh, S. B.; Majumdar, D.; Kim, K. S. Comparative ab initio study of the structures, energetics and spectra of X-(H2O)n=1-4 [X=F, Cl, Br, I] clusters. J. Chem. Phys.2000,113,5259-5272.
16. Vinogradov, S. N. Hydrogen bonds in crystal structures of amino acids, peptides and related molecules. Int. J. Pept. Protein Res.1979,14,281-289.
17. Zhang, W.; Piculell, L.; Nilsson, S. Effects of specific anion binding on the helix-coil transition of lower charged carrageenans. NMR data and conformational equilibria analyzed within the Poisson-Boltzmann cell model. Macromolecules 1992,25,6165-6172.
18. Washabaugh, M. W.; Collins, K. D. The systematic characterization by aqueous column chromatography of solutes which affect protein stability. J. Biol. Chem. 1986,261,12477-12485.
19. Chen, X.; Yang, T.; Kataoka, S.; Cremer, P. S. Specific ion effects on interfacial water structure near macromolecules. J. Am. Chem. Soc.2007,129, 12272-12279.
20. Lund, M.; Vrbka, L.; Jungwirth, P. Specific ion binding to nonpolar surface patches of proteins. J. Am. Chem. Soc.2008,130,11582-11583.
21. Ninham, B. W.; Yaminsky, V. Ion binding and ion specificity:the Hofmeister effect and Onsager and Lifshitz theories. Langmuir 1997,13,2097-2108.
22. Lund. M.; Jungwirth, P.; Woodward, C. E. Ion specific protein assembly and hydrophobic surface forces. Phys. Rev. Lett.2008,100,258105.
23. Heyda, J.; Hrobarik, T.; Jungwirth, P. Ion-specific interactions between halides and basic amino acids in water. J. Phys. Chem. A 2009,113,1969-1975.
24. Meyer, E. Internal water molecules and hydrogen bonding in biological macromolecules:a review of structural features with functional implications. Protein Sci.1992,1,1543-1562.
25. Sun, Y., Kollman, P. Are there water bridge-induced hydrophilic interactions. J. Phys. Chem.1996,100,6760-6763.
26. Zhou, P.; Lv, J.; Zou, J.; Tian, F.; Shang, Z. Halogen-water-hydrogen bridges in biomolecules. J. Struct. Biol.2010,169,172-182.
27. Rutenber, E.; Fauman, E. B.; Keenan, R. J.; Fong, S.; Furth, P. S.; Ortiz de Montellano, P. R.; Meng, E.; Kuntz, I. D.; DeCampn, D. L.; Saltoll, R.; Rosb, J. R.; Craik, C. S.; Stroud, R. M. Structure of a non-peptide inhibitor complexed with HIV-1 protease. Developing a cycle of structure-based drug design. J. Biol. Chem.1993,268,15343-15346.
28. Moller, C.; Plesset, M. S. Note on an approximation treatment for many-electron systems. Phys. Rev.1934,46,618-622.
29. Bader, R. F. W. Atoms in Molecules:A Quantum Theory; Oxford University Press:UK,1990.
30. Reed, A. E.; Curitss, L. A.; Weinhold, F. Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem. Rev.1988,88,889-926.
31. Raghavachari, K.; Trucks, G. W.; Pople, J. A.; Head-Gordon, M. A. A fifth-order perturbation comparison of electron correlation theories. Chem. Phys. Lett.1989, 157,479-483.
32. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor., Chim. Acta.1969,13,230-248.
33. Boys, S. F.; Bernardi, F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
34. Glukhovtsev, M. N.; Pross, A.; Radom, L. Gas-phase identity SN2 reactions of halide anions with methyl halides:a high-level computational study. J. Am. Chem. Soc.1995,117,2024-2032.
35. Sanov, A.; Faeder, J.; Parson, R.; Lineberger, W. C. Spin-orbit coupling in I·CO2 and I·OCS van der Waals complexes:beyond the pseudo-diatomic approximation. Chem.Phys.Lett.1999,3,3,812-819.
36.Cioslowski, J.; Piskorz, P. Properties of atoms in molecules from valence-electron densities augmented with core-electron contributions.Chem. Phys.Lett. 1996,255,315—319.
37.Asaduzzaman,A.M.;Schreckenbach,G.Computational study of the ground state properties of iodine and polyiodide ions.Theor.Chem.Account 2009,122, 119-125.
38.Vreven,T.;Byun,K.S.;Komaromi,I.;Dapprich,S.;Montgomery,J.A.; Morokuma,K.;Frisch,M.J.Combining quantum mechanics methods with molecular mechanics methods in ONIOM.J.Chem.Theory Comput.2006,2, 815-826.
39.Cornell,W.D.;Cieplak,P.;Bayly,C.I.;Gould,I.R.；Merz,Jr,K.M.;Ferguson, D.M.；Spellmeyer,D.C.；Fox,T.;Caldwell,J.W.;Kollman,P.A.A second generation force field for the simulation of proteins,nucleic acids,and organic molecules.J.Am.Chem.Soc.1995,117,5179-5197.
40.Jorgensen,W.L.;Chandrasekhar,J.;Madura,J.D.;Impey,R.W.;Klein,M.L. Comparison of simple potential functions for simulating liquid water.J.Chem. Phys.1983,79,926-935.
41.Comell,W.D.;Cieplak,P.；Bayly,C.I.;Kollman,P.A.Application of RESP charges to calculate conformational energies,hydrogen bond energies,and free energies of solvation.J.Am.Chem.Soc.1993,115,9620-9631.
42.Wang,J.;Wolf,R.M.;Caldwell,J.W.;Kollman,P.A.;Case,D.A.Developing and testing of a general amber force field.Comput.Chem.2004,25, 1157-1174.
43.Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.; Cheeseman,J.R.;Zakrzewski,V.G.;Montgomery,J.A.,Jr.;Stratmann,R.E.; Burant,J.C.;Dapprich,S.;Millam,J.M.;Daniels,A.D.;Kudin,K.N.;Strain, M.C.;Farkas,O.;Tomasi,J.;Barone,V.;Cossi,M.;Cammi,R.;Mennucci,B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T. Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L. Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 03; Gaussian, Inc.: Wallingford, CT,2003.
44. Biegler-Konig, F.; Schoenbohm, J. AIM2000,2.0 ed.; Buro fur Innovative Software:Bielefeld, Germany,2002.
45. Glendening, E. D.; Badenhoop, J, K.; Reed, A. E.; Carpente, J. E.; Bohmann, J. A.; Morales, C. M.; Weinhold, F. NBO 5.0; Theoretical Chemistry Institute, University of Wisconsin:Madison, WI,2001.
46. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
47. Krivov, G. G.; Shapovalov, M. V.; Dunbrack Jr., R. L. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 2009,77,778-795.
48. Kabsch, W.; Sander, C. Dictionary of protein secondary structure:pattern recognition of hydrogen-bonded and geometricalal features. Biopolymers 1983, 22,2577-2637.
49. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
50. Bas, D. C.; Rogers, D. M.; Jensen, J. H. Very fast prediction and rationalization of pKa values for protein-ligand complexes. Proteins 2008,73,765-783.
51. Zhao, Y.; Cheng, T.; Wang, R. Automatic perception of organic molecules based on essential structural information. J. Chem. Inf. Model.2007,47,1379-1385.
52. Sanner, M. F.; Olson, A. J.; Spehner, J.-C. Reduced surface:an efficient way to compute molecular surfaces. Biopolymers 1996,38,305-320.
53. Rother, K.; Hildebrand, P. W.; Goede, A.; Gruening, B.; Preissner, R. Voronoia: analyzing packing in protein structures. Nucleic Acids Res.2009,37, D393-D935.
54. Tsai, J.; Taylor, R.; Chothia, C.; Gerstein, M. The packing density in proteins: standard radii and volumes. J. Mol. Biol.1999,290,253-266.
55. Shannon, R. D. Revised effective ionic radii and systematic studies of interatomic distances in halides and chaleogenides. Acta Cryst.1976, A32, 751-767.
56. Ooi, T.; Oobatake, M.; Nemethy, G.; Scheraga, H. A. Accessible surface areas as a measure of the thermodynamic parameters of hydration of peptides. Proc. Natl. Acad. Sci. USA 1987,84,3086-3090.
57. Klots, C. E. Solubility of protons in water. J. Phys. Chem.1981,85,3585-3588.
58. Meot-Ner, M. The ionic hydrogen bond. Chem. Rev.2005,105,213-284.
59. Nakanishi, W.; Hayashi, S.; Narahara, K. Atoms-in-molecules dual parameter analysis of weak to strong interactions:behaviors of electronic energy densities versus Laplacian of electron densities at bond critical points.J. Phys. Chem. A 2008,112,13593-13599.
60. Wiberg, K. B. Application of the pople-santry-segal CNDO method to the cyclopropylcarbinyl and eyelobutyl cation and to bicyelobutane. Tetrahedron 1968,24,1083-1096.
61. Reed, A. E.; Schleyer, P. The anomeric effect with central atoms other than carbon.2. Strong interactions between nonbonded substituents in mono-and polyfluorinated first- and second-row amines, FnAHmNH2. Inorg. Chem.1988,27, 3969-3987.
62. Chesnut D. B. A simple definition of ionic bond order. J. Chem. Theory Comput. 2008,4,1637-1642.
63. Prabakaran, P.; Singarayan, M. G. Long-range ordering in water-halide ion interactions:a database study. Chem. Lett.2004,33,1640-1641.
64. Rajagopal, S.; Vishveshwara, S. Short hydrogen bonds in proteins. FEBS J.2005, 272,1819-1832.
65. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl. Acad. Sci. USA 2004,101,16789-16794.
66. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol. 1999,293,1241-1255.
67. Baldwin, R. L. Rose, G. D. Is protein folding hierarchic? Ⅱ. Folding intermediates and transition states. Trends Biochem. Sci.1999,24,77-84.
68. Tsai, C. J.; Xu, D.; Nussinov, R. Protein folding via binding and vice versa, Fold. Des.1998,3, R71-R80.
69. Lu, Y.; Wang, R.; Yang, C. Y.; Wang, S. Analysis of ligand-bound water molecules in high-resolution crystal structures of protein-ligand complexes. J. Chem. Inf. Model.2007,47,668-675.
70. Srinivasan, R.; Rose, G. D. A physical basis for protein secondary structure. Proc. Natl. Acad. Sci. USA 1999,96,14258-14263.
71. Lu, Y.; Shi, T.; Wang, Y.; Yang, H.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. Halogen bonding-a novel interaction for rational drug design. J. Med. Chem.2009,52, 2854-2862.
72. Lu, Y.; Wang, Y.; Xu, Z.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. C-X…H contacts in biomolecular systems:how they contribute to protein-ligand binding affinity. J. Phys. Chem. B 2009,113,12615-12621.
73. Alzate-Morales, J. H.; Caballero, J.; Jague, A. V.; Nilo, F. D. G. Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors:prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculation.J. Chem. Inf. Model.2009,49, 886-899.
74. Feldman, R. I.; Wu, J. M.; Polokoff, M. A. Kochanny, M. J.; Dinter, H.; Zhu, D.; Biroc, S. L.; Alicke, B.; Bryant, J.; Yuan, S.; Buckman, B. O.; Lentz, D.; Ferrer, M.; Whitlow, M.; Adler, M.; Finster, S.; Chang, Z.; Arnaiz, D. O. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem. 2005,280,19867-19874.
75. Word, J. M.; Lovell, S. C.;, LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol.1999,285,1711-1733.
76. Zhou, P.; Tian, F.; Zou, J.; Shang Z. Rediscovery of halogen bonds in protein-ligand complexes. Mini Rev. Med. Chem.2010,10,309-314.
77. Bondi, A. van der Waals volumes and radii. J. Phys. Chem.1964,68,441-451.
1. Zhou, P.; Tian, F.; Zou, J.; Ren, Y.; Liu, X.; Shang, Z. Do halide motifs stabilize protein architecture? J. Phys. Chem. B 2010,114,15673-15686.
2. Lund. M.; Jungwirth, P.; Woodward, C. E. Ion specific protein assembly and hydrophobic surface forces. Phys. Rev. Lett.2008,100,258105.
3. Bostrom, M.; Williams, D.; Ninham, B. W. Specific ion effects:why DLVO theory fails for biology and colloid systems. Phys. Rev. Lett.2001,87,168103.
4. Kumar, S.; Nussinov, R. Close-range electrostatic interactions in proteins. ChemBioChem 2002,3,604-617.
5. Pervushin, K.; Billeter, M.; Siegal, G.; Wuthrich, K. Structural role of a buried salt bridge in the 434 repressor DNA-binding domain. J. Mol. Biol.1996,264, 1002-1012.
6. Lounnas, V.; Wade, R. C. Exceptionally stable salt bridges in cytochrome P450cam have functional roles. Biochemistry 1997,36,5402-5417.
7. Singh, U. C. Probing the salt bridge in the dihydrofolate reductase-methotrexate complex by using the coordinate-coupled free energy perturbation method. Proc. Natl Acad. Sci. USA 1988,85,4280-4284.
8. Sun, D. P.; Sauer, U.; Nicholson, H.; Matthews, B. W. Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. Biochemistry 1991,30,7142-7153.
9. Waldburger, C. D.; Schildbach, J. F.; Sauer, R. T. Are buried salt bridges important for protein stability and conformational specificity? Nat. Struct. Biol. 1995,2,122-128.
10. Netz, R. R. Water and ions at interfaces. Curr. Opin. Colloid Interface Sci.2004, 9,192-197.
11. Mahanty, J.; Ninham, B. W. Dispersion Forces; London:Academic Press, 1976.
12. Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S. H.; Chong, L.; Lee, M.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J., Case, D. A.; Cheatham, T. E. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc. Chem. Res.2000, 33,889-897.
13. Menikarachchi, L. C.; Gascon, J. A. QM/MM approaches in medicinal chemistry research. Curr. Top. Med. Chem.2010,10,46-54.
14. Krivov, G. G.; Shapovalov, M. V.; Dunbrack Jr, R. L. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 2009,77,778-795.
15. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
16. Bas, D. C.; Rogers, D. M.; Jensen, J. H. Very fast prediction and rationalization of pKa values for protein-ligand complexes. Proteins 2008,73,765-783.
17. Derjaguin, B. V. On the role of electrostriction terms in ionic electrostatic repulsion electrostatic component of the disjoining pressure. J. Colloid Interface Sci.1976,56,492-494.
18. Sizonenko, V. L. The role of image charge in ionic-electrostatic interactions of proteins and membranes. Biofizika 1995,40,1251-1255.
19. Ninham, B. W.; Yaminsky, V. Ion binding and ion specificity:the Hofmeister effect and Onsager and Lifshitz theories. Langmuir 1997,13,2097-2108.
20. Eriksson, A. E.; Baase, W. A.; Zhang, X. J.; Heinz, D. W.; Blaber, M.; Baldwin, E. P.; Matthews, B. W. Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. Science 1992,255, 178-183.
21. Rocchia, W.; Alexov, E.; Honig, B. Extending the applicability of the nonlinear. Poisson-Boltzmann equation:multiple dielectric constants and multivalent ions. J. Phys. Chem.2001,105,6507-6514.
22. Gilson, M. K.; Sharp, K. A.; Honig, B. H. Calculating the electrostatic potential of molecules in solution:method and error assessment. J. Comput. Chem.1987, 9,327-335.
23. Sitkoff, D.; Sharp, K. A.; Honig, B. Accurate calculation of hydration free energies using macroscopic solvent models. J. Phys. Chem.1994,98, 1978-1988.
24. Noyes, R. Thermodynamics of ion hydration as a measure of effective dielectric properties of water. J. Am. Chem. Soc.1962,84,513-522.
25. Rashin, A. A.; Honig, B. Reevaluation of the Born model of ion hydration. J. Phys. Chem.1985,89,5588-5593.
26. Bostrom, M.; Ninham, B. W. Contributions from dispersion and Born self-free energies to the solvation energies of salt solutions. J. Phys. Chem. B 2004,108, 12593-12595.
27. Stokes, R. H. The van der Waals radii of gaseous ions of the noble gas structure in relation to hydration energies.J. Am. Chem. Soc.1964,86,979-982.
28. Nagle. J. K. Atomic polarizability and electronegativity. J. Am. Chem. Soc.1990, 112,4141-4141.
29. Parsons, D. F.; Ninham, B. W. Importance of accurate dynamic polarizabilities for the ionic dispersion interactions of alkali halides. Langmuir 2010,26, 1816-1823.
30. Lide, D. R. CRC Handbook of Chemistry and Physics,84th Edition; Florida: CRC Press,2003.
31. Marcus, Y. Ion Properties; New York:Marcel Dekker Press,1997.
32. Bostrom, M.; Ninham. B. W. Dispersion self-free energies and interaction free energies of finite-sized ions in salt solutions. Langmuir 2004,20,7569-7574.
33. Bostrom, M.; Ninham. B. W. Energy of an ion crossing a low dielectric membrane:the role of dispersion self-free energy. Biophys. Chem.2005,114, 95-101.
34. Boroudjerdi, H.; Kim, Y. W.; Naji, A.; Netz, R. R.; Schlagberger, X.; Serr. A. Statics and dynamics of strongly charged soft matter. Phys. Rep.2005,416, 129-199.
35. Sanner, M. F.; Olson, A. J.; Spehner, J. C. Reduced surface:an efficient way to compute molecular surfaces. Biopolymers 1996, 38, 305-320.
36.Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J. Chem. Theory Comput. 2006, 2, 815-826.
37.Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T. Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 03; Gaussian, Inc.: Wallingford, CT, 2003.
38.Curtiss, L. A.; Raghavachari, K.; Trucks, G. W.; Pople, J. A. Gaussian-2 theory for molecular energies of first- and second-row compounds. J. Chem. Phys. 1991, 94, 7221-7230.
39.Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, Jr, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 1995,117, 5179-5197.
40.Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L, Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926-935.
41.Joung, I. S.; Cheatham Ⅲ, T. E. Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations. J. Phys. Chem. B 2008,112,9020-9041.
42. Kristyan, S.; Pulay, P. Can (semi) local density functional theory account for the London dispersion forces? Chem. Phys. Lett.,1994,229,175-180.
43. Johnson, E. R.; Wolkow, R. A.; DiLabio, G. A. Application of 25 density functionals to dispersion-bound homomolecular dimers. Chem. Phys. Lett.2004, 394,334-338.
44. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor. Chim. Acta.1969,13,230-248.
45. Boys, S. F.; Bernardi, F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
46. Janssen, D. B. Evolving haloalkane dehalogenases. Curr. Opin. Chem. Biol. 2004,8,150-159.
47. Verschueren, K. H. G.; Seljee, F.; Rozeboom, H. J.; Kalk, K. H.; Dijkstra, B. W. Crystallographic analysis of the catalytic mechanism of haloalkane dehalogenase. Nature 1993,363,693-698.
48. Schanstra, J. P.; Kingma, J.; Janssen, D. B. Specificity and kinetics of haloalkane dehalogenase. J. Biol. Chem.1996,271,14747-14753.
49. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
50. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol.1999,293,1241-1255.
51. Bostrom, M.; Williams, D. R. M.; Ninham, B. W. Specific ion effects:why the properties of lysozyme in salt solutions follow a Hofmeister series. Biophys. J. 2003,85,686-694.
52. Hendsch, Z. S.; Tidor, B. Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Sci.1994,3,211-226.
53. Zhou, P.; Ren, Y.; Tian, F.; Zou, J.; Shang, Z. Halogen-ionic bridges:do they exist in the biomolecular world? J. Chem. Theory Comput.2010,6,2225-2241.
54. Amico, D.; Gerday, S. C.; Feller, G. Structural similarities and evolutionary relationships in chloride-dependent a-amylases. Gene 2000,253,95-105.
55. Lesley, S. A.; Kuhn, P.; Godzik, A.; Deacon, A. M.; Mathews, I.; Kreusch, A.; Spraggon, G.; Klock, H. E.; McMullan, D.; Shin, T.; Vincent, J.; Robb, A.; Brinen, L. S.; Miller, M. D.; McPhillips, T. M.; Miller, M. A.; Scheibe, D.; Canaves, J. M.; Guda, C.; Jaroszewski, L.; Selby, T. L.; Elsliger, M.; Wooley, J.; Taylor, S. S.; Hodgson, K. O.; Wilson, I. A.; Schultz, P. G.; Stevens, R. C. Structural genomics of the Thermotoga maritime proteome implemented in a high-throughput structure determination pipeline. Proc. Natl Acad. Sci. USA 2002,99,11664-11669.
56. Pikkemaat, M. G.; Ridder, I. S.; Rozeboom, H. J.; Kalk, K. H.; Dijkstra, B. W.; Janssen, D. B. Crystallographic and kinetic evidence of a collision complex formed during halide import in haloalkane dehalogenase. Biochemistry 1999,38, 12052-12061.
57. Dagastine, R. R.; Prieve, D. C.; White, L.R. The dielectric function for water and its application to van der Waals forces. J. Colloid Interface Sci.2000,231, 351-358.
58. Ninham, B. W.; Parsegian, V. A. van der Waals forces. Special characteristics in lipid-water systems and a general method of calculation based on the Lifshitz theory. Biophys. J.1970,10,646-663.
59. Israelachvili, J. N. Intermolecular and Surface Forces; London:Academic Press, 1992.
60. Tavares, F. W.; Bratko, D.; Blanch, H. W.; Prausnitz. J. M. Ion-specific effects in the colloid-colloid or protein-protein potential of mean force:role of salt-macroion van der Waals interactions. J. Phys. Chem. B 2004,108, 9228-9235.
1. Zhou, P.; Tian, F.; Shang, Z.2D depiction of nonbonding interactions for protein complexes. J. Comput. Chem.2009,30,940-951.
2. Zhou, P.; Shang, Z.2D molecular graphics:a flattened world of chemistry and biology. Brief. Bioinform.2009,10,247-258.
3. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
4. Bader, G. D.; Hogue, C. W. BIND—a data specification for storing and describing biomolecular interactions, molecular complexes and pathways. Bioinformatics 2000,16,465-477.
5. Xenarios, I.; Rice, D. W.; Salwinski, L.; Baron, M. K.; Marcotte, E. M.; Eisenberg, D. DIP:the database of interacting proteins. Nucleic Acids Res.2000, 28,289-291.
6. Fischer, T. B.; Arunachalam, K. V.; Bailey, D.; Mangual, V.; Bakhru, S.; Russo, S.; Huang, D.; Paczkowski, M.; Lalchandani, V.; Ramachandra, C.; Ellison, B.; Galer, S.; Shapley, J.; Fuentes, E.; Tsai, J. The binding interface database (BID): a compilation of amino acid hot spots in protein interfaces. Bioinformatics 2003, 19,1453-1454.
7. Xenarios, I.; Eisenberg, D. Protein interaction databases. Curr. Opin. Biotech. 2001,12,334-339.
8. Dutta, S.; Berman, H. M. Large macromolecular complexes in the protein data bank:a status report. Structure 2005,13,381-388.
9. Clackson, T.; Wells, J. A. A hot spot of binding energy in a hormone-receptor interface. Science 1995,267,383-386.
10. Lawrence, M. C.; Colman, P. M. Shape complementarity at protein/protein interfaces. J. Mol. Biol.1993,234,946-950.
11. Aloy, P.; Russell, R. B. Ten thousand interactions for molecular biologist. Nat. Biotech.2004,22,1317-1321.
12. Chothia, C.; Janin, J. Principles of protein-protein recognition. Nature 1974, 256,705-708.
13. Horn, J. R.; Ramaswamy, S.; Murphy, K. P. Structure and energetics of protein-protein interactions:the role of conformational heterogeneity in OMTKY3 binding to serine proteases. J. Mol. Biol.2003,331,497-508.
14. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT:a program to generate schematic diagrams of protein-ligand interactions. Protein Eng.1995, 8,127-134.
15. Stierand, K.; MaaB, P. C.; Rarey, M. Molecular complexes at a glance: automated generation of two-dimensional complex diagrams. Bioinformatics 2006,22,1710-1716.
16. Clark, A. M.; Labute, P.2D depiction of protein-ligand complexes. J. Chem. Inf. Model.2007,47,1933-1944.
17. Luscombe, N. M.; Laskowski, R. A.; Thornton, J. M. NUCPLOT:a program to generate schematic diagrams of protein-nucleic acid interactions. Nucleic Acids Res.1997,25,4940-4945.
18. Finn, R. D.; Marshall. M.; Bateman, A. iPfam:visualization of protein-protein interactions in PDB at domain and amino acid resolutions. Bioinformatics 2005, 27,410-412.
19. Salerno, W. J.; Seaver, S. M.; Armstrong, B. R.; Radhakrishnan, I. MONSTER: inferring non-covalent interactions in macromolecular structures from atomic coordinate data. Nucleic Acids Res.2004,32, W566-W568.
20. Mancini, A. L.; Higa, R. H.; Oliveira, A.; Dominiquini, F.; Kuser, R. R.; Yamagishi, M. E. B.; Togawa, R. C.; Neshich, G. STING contacts:a web-based application for identification and analysis of amino acid contacts within protein structure and across protein interfaces. Bioinformatics 2004,20,2145-2147.
21. Sobolev, V.; Sorokine, A.; Prilusky, J.; Abola, E. E.; Edelman, M. Automated analysis of interatomic contacts in proteins. Bioinformatics 1999,15, 327-332.
22. Fischer, T. B.; Holmes, J. B.; Miller, I. R.; Parsons, J. R.; Tung, L.; Hu, J. C.; Tsai, J. Assessing methods for identifying pair-wise atomic contacts across binding interfaces. J. Struct. Biol.2006,153,103-112.
23. McConkey, B. J.; Sobolev, V.; Edelman, M. Quantification of protein surfaces, volumes and atom-atom contacts using a constrained Voronoi procedure. Bioinformatics 2002,18,1365-1373.
24. Cootes, A. P.; Curmi, P. M. G.; Cunningham, R.; Donnelly, C.; Torda, A. E. The dependence of amino acid pair correlations on structural environment. Proteins 1998,32,175-189.
25. Reva, B. A.; Finkelstein, A. V.; Sanner, M. F.; Olson, A. J. Residue-residue mean-force potentials for protein structure recognition. Protein Engin.1997,10, 865-876.
26. Williams, G.; Doherty, P. Inter-residue distances derived from fold contact propensities correlate with evolutionary substitution costs. BMC Bioinformatics 2004,5,153.
27. Kazmierkiewicz, R.; Liwo, A.; Scherag, H. A. Addition of side chains to a known backbone with defined side chain centroids. Biophys. Chem.2003,100, 261-280.
28. Zhou, H.; Zhou, Y. Stability scale and atomic solvation parameters extracted from 1023 mutation experiments. Proteins 2002,49,483-492.
29. Zhang, C.; Vasmatzis, G.; Cornette, J. L.; DeLisi C. Determination of atomic desolvation energies from the structures of crystallized proteins. J. Mol. Biol. 1997,267,707-726.
30. Lo Conte, L.; Chothia, C.; Janin, J. The atomic structure of protein-protein recognition sites. J. Mol. Biol.1999,285,2177-2198.
31. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
32. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins. J. Mol. Biol.1994,238,777-793.
33. Word, J. M.; Lovell, S. C.; LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol. 1999,285,1711-1733.
34. Sanner, M. F.; Olson, A. J.; Spehner, J. C. Reduced surface:an efficient way to compute molecular surfaces. Biopolymers 1996,38,305-320.
35. Rocchia, W.; Alexov, E.; Honig B. Extending the applicability of the nonlinear Poisson-Boltzmann equation:multiple dielectric constants and multivalent ions. J. Phys. Chem. B 2001,105,6507-6514.
36. Vriend, G. WHATIF:a molecular modeling and drug design program. J. Mol. Graph.1990,8,52-56.
37. Canutescu, A. A.; Shelenkov, A. A.; Dunbrack Jr, R. L. A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci.2003,12, 2001-2014.
38. Brunger, A. T.; Kuriyan, J.; Karplus, M. Crystallographic R factor refinement by molecular dynamics. Science 1987,235,458-460.
39. Boobbyer, D. N. A.; Goodford, P. J.; McWhinnie, P. M.; Wade, R. C. New hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structure. J. Med. Chem.1989,32,1083-1094.
40. Goodford, P. J. A computational procedure for determining energetically favorable binding sites on biologically important molecules. J. Med. Chem. 1985,28,849-857.
41. Vedani, A.; Dunitz, J. D. Lone-pair directionality in hydrogen bond potential functions for molecular mechanics calculations. J. Am. Chem. Soc.1985,107, 7653-7658.
42. Brooks, B. R.; Bruccoleri, R.E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. CHARMM:a program for macromolecular energy, minmimization, and dynamics calculations. J. Comput. Chem.1983,4,187-217.
43. Huey, R.; Morris, G. M.; Olson, A. J.; Goodsell, D. S. A semiempirical free energy force field with charge-based desolvation. J. Comput. Chem.2007,28, 1145-1152.
44. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz Jr, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc.1995,117,5179-5197.
45. Hirschfelder, J.; Roseveare, W. Intermolecular forces and the properties of gases. J. Phys. Chem.1939,43,15-35.
46. de Vries, S. J.; Bonvin, A. M. J. Intramolecular surface contacts contain information about protein-protein interface regions. Bioinformatics 2006,22, 2094-2098.
47. Bondi, A. van der Waals volumes and radii.J. Phys. Chem.1964,68,441-451.
48. Chothia, C. Structural invariants in protein folding. Nature 1975,254,304-308.
49. Li, A. J.; Nussinov, R. A set of van der Waals and Coulombic radii of protein atoms for molecular and solvent-accessible surface calculation, packing evaluation, and docking. Proteins 1998,32,111-127.
50. Eisenberg, D.; McLachlan, A. D. Solvation energy in protein folding and binding. Nature 1986,319,199-203.
51. Juffer, A. H.; Eisenhaber, F.; Hubbard, S. J.; Walther, D.; Argos, P. Comparison of atomic solvation parametric sets:applicability and limitations in protein folding and binding. Protein Sci.1995,4,2499-2509.
52. Kim, A. Amino acid side chain contributions to free energy of transfer of tripeptides from water to octanol [dissertation]. San Francisco, California: University of California,1990.
53. Schiffer, C. A.; Caldwell, J. W.; Kollman, P. A.; Stroud, R. M. Protein structure prediction with a combined solvation free energy-molecular mechanics force field. Mol. Simul.1993,10,121-149.
54. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol.1999,293,1241-1255.
55. Kumar, S.; Nussinov, R. Close range electrostatic interactions in proteins. ChemBioChem 2002,3,604-617.
56. Sarakatsannis, J. N.; Duan, Y. Statistical characterization of salt bridges in proteins. Proteins 2005,60,732-739.
57. Hendsch, Z. S.; Tidor, B. Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Sci.1994,3,211-226.
58. Hendsch, Z. S.; Sindelar, C. V.; Tidor, B. Parameter dependence in continuum electrostatic calculations:a study using protein salt bridges J. Phys. Chem. B 1998,102,4404-4410.
59. Sitkoff, D.; Sharp, K. A.; Honig, B. Accurate calculation of hydration free energies using macroscopic solvent models. J. Phys. Chem.1994,98, 1978-1988.
60. Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta Jr, S.; Weiner, P. A new force field for molecular mechanical simulation of nucleic acids and proteins. J. Am. Chem. Soc.1984,106,765-784.
61. MacKerell Jr, A. D.; Bashford, D.; Bellott, M.; Dunbrack Jr, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher Ⅲ, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 1998,102,3586-3616.
62. Kumar, S.; Nussinov, R. Relationship between ion pair geometries and electrostatic strengths in proteins. Biophys. J.2002,83,1595-1612.
63. D'Aquino, J. A.; Gomez, J.; Hilser, V. J.; Lee, K. H.; Amzel, L. M.; Fieire, E. The magnitude of the backbone conformational entropy change in protein folding. Proteins 1996,25,143-156.
64. Brady, G. P.; Sharp, K. A. Entropy in protein folding and in protein-protein interactions. Curr. Opin. Struct. Biol.1997,7,215-221.
65. Doig, A. J.; Sternberg, M. J. E. Side-chain conformational entropy in protein folding. Protein Sci.1995,4,2247-2251.
66. Creamer, T. P. Side-chain conformational entropy in protein unfolded states. Proteins 2000,40,443-450.
67. Koehl, P.; Delarue, M. Application of a self consistent mean field theory to predict protein side-chain conformations and estimate their conformational entropy. J. Mol. Biol.1994,239,249-275.
68. Karplus, M.; Ichiye, T.; Pettitt, B. M. Configurational entropy of native proteins. Biophys. J.1987,52,1083-1085.
69. Chellgren, B. W.; Creamer, T. P. Side-chain entropy effects on protein secondary structure formation. Proteins 2006,62,411-420.
70. Lovell, S. C.; Word, J. M.; Richardson, J. S.; Richardson, D. C. The penultimate rotamer library. Proteins 2000,40,389-408.
71. Dunbrack Jr, R. L. Rotamer libraries in the 21st century. Curr. Opin. Struct. Biol. 2002,12,431-440.
72. Zhang, J.; Liu, J. S. On side-chain conformational entropy of proteins. PLoS Comput. Biol.2006,2,1586-1591.
73. Chowdry, A. B.; Reynolds, K. A.; Hanes, M. S.; Voorhies, M.; Pokala, N.; Handel, T. M. An object-oriented library for computational protein design. J. Comput. Chem.2007,28,2378-2388.
74. Tsai, J.; Taylor, R.; Chothia, C.; Gerstein, M. The packing density in proteins: standard radii and volumes. J. Mol. Biol.1999,290,253-266.
75. McGaughey, G. B.; Gagne, M.; Rappe, A. K. p-stacking interactions, alive and well in protein. J. Boil. Chem.1998,273,15458-15463.
76. Cho, K.; Lee, K.; Lee, K. H.; Kim, D.; Lee, D. Specificity of molecular interactions in transient protein-protein interaction interfaces. Proteins 2006,65, 593-606.
77. Sun, S.; Bernstein, E. R. Aromatic van der Waals clusters:structure and nonrigidity. J. Phys. Chem.1996,100,13348-13366.
2. Perutz, M. F.; Kendrew, J. C. Nobel Lecture:Myoglobin and the Structure of Proteins; 1962.
3. Barabasi, A.-L.; Oltvai, Z. N. Network biology:understanding the cell's functional organization. Nat. Rev.2004,5,101-113.
4. Gomase, V. S.; Changbhale, S. S.; Patil, S. A.; Kale, K. V. Metabolomics. Curr. Drug Metab.2008,9,89-98.
5. Ideker, T.; Galitski, T.; Hood, L. A new approach to decoding life:systems biology. Annu. Rev. Genomics Hum. Genet.2001,2,343-372.
6. Andrianantoandro, E.; Basu, S.; Karig, D. K.; Weiss, R. Synthetic biology:new engineering rules for an emerging discipline. Mol. Syst. Biol.2006,2, 2006.0028.
7. Lawrence, M. C.; Colman, P. M. Shape complementarity at protein/protein interfaces.J. Mol. Biol.1993,234,946-950.
8. Clackson, T.; Wells, J. A. A hot spot of binding energy in a hormone-receptor interface. Science 1995,267,383-386.
9. Wear, M. A.; Kan, D.; Rabu, A.; Walkinshaw, M. D. Experimental determination of van der Waals energies in a biological system. Angew. Chem. Int. Ed.2007,119,6573-6576.
10. Chen, C. M. Lattice model of transmembrane polypeptide folding. Phys. Rev. 2001,63,010901R.
11. Errington, N.; Doig, A. J. A phosphoserine-lysine salt bridge within an a-helical peptide, the strongest a-helix side-chain interaction measured to date. Biochemistry 2005,44,10449-10456.
12. Gervasio, F. L.; Chelli, R.; Procacci, P.; Schettino, V. The nature of intermolecular interactions between aromatic amino acid residues. Proteins 2002,48,117-125.
13. Desiraju, G. R. Hydrogen bridges in crystal engineering:interactions without borders. Ace. Chem. Res.2002,35,565-573.
14. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based recognition processes:a world parallel to hydrogen bonding. Ace. Chem. Res. 2005,38,386-395.
15. Green, D. E.; Zande, H. D. V. Universal energy principle of biological systems and the unity of bioenergetics. Proc. Natl. Acad. Sci. USA 1981,78,5344-5347.
16. Latimer, W. M.; Rodebush, W. H. Polarity and ionization from the standpoint of the Lewis theory of valence. J. Am. Chem. Soc.1920,42,1419-1433.
17. Pauling, L. The Nature of the Chemical Bond; Ithaca:Cornell University Press, 1960.
18. Pauling, L.; Corey, R. B.; Branson, H. R. Two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl Acad. Sci. USA 1951,37, 205-211.
19. Watson J. D.; Crick F. H. C. A structure for deoxyribose nucleic acid. Nature 1953,171,737-738.
20. Fershta A. R. The hydrogen bond in molecular recognition. Trends Biochem. Sci.1987,12,301-304.
21. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based recognition processes:a world parallel to hydrogen bonding. Acc. Chem. Res. 2005,38,386-395.
22. Clark, T.; Hennemann, M.; Murray, J. S.; Politzer, P. Halogen bonding:the s-hole. J. Mol. Model.2007,13,291-296.
23. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl Acad. Sci. USA 2004,101,16789-16794.
24. Voth, A. R.; Hays, F. A.; Ho, P. S. Directing macromolecular conformation through halogen bonds. Proc. Natl Acad. Sci. USA 2007,104,6188-6193.
25. Lu, Y.; Shi, T.; Wang, Y.; Yang, H.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. Halogen bonding—a novel interaction for rational drug design? J. Med. Chem. 2009,52,2854-2862.
26. Jeschke, P. The unique role of halogen substituents in the design of modern agrochemicals. Pest Manag. Sci.2010,66,10-27.
27. Riley, K. E.; Murray, J. S.; Politzer, P.; Concha, M. S.; Hobza, P. Br…O complexes as probes of factors affecting halogen bonding:interactions of bromobenzenes and bromopyrimidines with acetone. J. Chem. Theory Comput. 2009,5,155-163.
28. Voth, A. R.; Khuu, P.; Oishi, K.; Ho, P. S. Halogen bonds as orthogonal molecular interactions to hydrogen bonds. Nat. Chem.2009,1,74-79.
29. Lu, Y.; Wang, Y.; Xu, Z.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. C-X…H contacts in biomolecular systems:how they contribute to protein-ligand binding affinity. J. Phys. Chem. B 2009,113,12615-12621.
30. Lu, Y.; Wang, Y.; Zhu, W. Nonbonding interactions of organic halogens in biological systems:implications for drug discovery and biomolecular design. Phys. Chem. Chem. Phys.2010,12,4543-4551.
31. Zhou, P.; Tian, F.; Zou, J.; Shang, Z. Rediscovery of halogen bonds in protein-ligand complexes. Mini Rev. Med. Chem.2010,10,309-314.
32. Kraut, D. A.; Churchill, M. J.; Dawson, P. E.; Herschlag, D. Evaluating the potential for halogen bonding in the oxyanion hole of ketosteroid isomerase using unnatural amino acid mutagenesis. ACS Chem. Biol.2009,4,269-273.
33. Kumar, S.; Nussinov, R. Close-range electrostatic interactions in proteins. ChemBioChem 2002,3,604-617.
34. Marqusee, S.; Sauer, R. T. Contribution of a hydrogen bond/salt bridge network to the stability of secondary and tertiary structures in lambda repressor. Protein Sci.1994,3,2217-2225.
35. Pervushin, K.; Billeter, M.; Siegal, G.; Wuthrich, K. Structural role of a buried salt bridge in the 434 repressor DNA-binding domain. J. Mol. Biol.1996,264, 1002-1012.
36. Lounnas, V.; Wade, R. C. Exceptionally stable salt bridges in cytochrome P450cam have functional roles. Biochemistry 1997,36,5402-5417.
37. Singh, U. C. Probing the salt bridge in the dihydrofolate reductase-methotrexate complex by using the coordinate-coupled free energy perturbation method. Proc. Natl. Acad. Sci. USA 1988,85,4280-4284.
38. Barril, X.; Aleman, C.; Orozco, M.; Luque, F. J. Salt bridge interactions: stability of ionic and neutral complexes in the gas phase, in solution and in proteins. Proteins 1998,32,67-79.
39. Sun, D. P.; Sauer, U.; Nicholson, H.; Matthews, B. W. Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. Biochemistry 1991,30,7142-7153.
40. Waldburger, C. D.; Schildbach, J. F.; Sauer, R. T. Are buried salt bridges important for protein stability and conformational specificity? Nat. Struct. Biol. 1995,2,122-128.
41. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol.1999,293,1241-1255.
42. Delcourt, S. G.; Blake, R. D. Stacking energies in DNA. J. Biol. Chem.1991, 266,15160-15169.
43. Cheng, Y. K.; Pettitt, B. M. Stabilities of double- and triple-strand helical nucleic acids. Prog. Biophys. Mol. Biol.1992,58,225-257.
44. Sponer, J.; Gabb, H. A.; Leszczynski, J.; Hobza, P. Base-base and deoxyribose-base stacking interactions in B-DNA and Z-DNA:a quantum-chemical study. Biophys. J.1997,73,76-87.
45. Ryeha, D.; Kabelac, M.; Ryjacek, F.; Syponer, J.; Syponer, J. E.; Elstner, M.; Suhai, S.; Hobza, P. Intercalators.1. Nature of stacking interactions between intercalators (ethidium, daunomycin, ellipticine, and 4',6-diaminide-2-phenylindole) and DNA base pairs. Ab initio quantum chemical, density functional theory, and empirical potential study. J. Am. Chem. Soc 2002,124,3366-3376.
46. Manalo, M. N.; Perez, L. M.; Wang, A. L. Hydrogen-bonding and p-p base-stacking interactions are coupled in DNA, as suggested by calculated and experimental trans-H-bond deuterium isotope shifts. J. Am. Chem. Soc.2007, 129,11298-11299.
47. Li, S.; Cooper, V. R.; Thonhauser, T.; Lundqvist, B. I.; Langreth, D. C. Stacking interactions and DNA intercalation. J. Phys. Chem. B 2009,113, 11166-11172.
48. McGaughey, G. B.; Gagne, M.; Rappe, A. K. p-stacking interactions. Alive and well in proteins. J. Biol. Chem.1998,273,15458-15463.
49. Gervasio, F. L.; Chelli, R.; Procacci, P.; Schettino, V. The nature of intermolecular interactions between aromatic amino acid residues. Proteins 2002,48,117-125.
50. Chelli, R.; Gervasio, F. L.; Procacci, P.; Schettino, V. Stacking and T-shape competition in aromatic-aromatic amino acid interactions. J. Am. Chem. Soc., 2002,124,6133-6143.
51. Rutledge, L. R.; Wetmore, S. D. Remarkably strong T-shaped interactions between aromatic amino acids and adenine:their increase upon nucleobase methylation and a comparison to stacking. J. Chem. Theory Comput.2008,4, 1768-1780.
52. Dougherty, D. A. Cation-p interactions in chemistry and biology:a new view of benzene, Phe, Tyr, and Trp. Science 1996,271,163-168.
53. Gallivan, J. P.; Dougherty, D. A. Cation-p interactions in structural biology. Proc. Natl Acad. Sci. USA 1999,96,9459-9464.
54. Crowley, P. B.; Golovin, A. Cation-p interactions in protein-protein interfaces. Proteins 2005,59,231-239.
55. Wintjens, R.; Lievin, J.; Rooman, M.; Buisine, E. Contribution of cation-p interactions to the stability of protein-DNA complexes. J. Mol. Biol.2000,302, 393-408.
56. Scharer, K.; Morgenthaler, M.; Paulini, R.; Obst-Sander, U.; Banner, D. W.; Schlatter, D.; Benz, J.; Stihle, M.; Diederich, F. Quantification of cation-p interactions in protein-ligand complexes:crystal structure analysis of factor Xa bound to a quaternary ammonium ion ligand. Angew. Chem. Int. Ed.2005,44, 4400-4404.
57. Garde, S.; Hummer, G.; Garcia, A. E.; Paulaitis, M. E.; Pratt, L. R. Origin of entropy convergence in hydrophobic hydration and protein folding. Phys. Rev. Lett.1996,77,4966-4968.
58. Jungwirth, P.; Zahradnik, R. The entropy driven hydrophobic effect as a function of solute—solvent interactions. A molecular dynamics study. Chem. Phys. Lett.1994,217,319-324.
59. Tsai, C. J.; Lin, S. L.; Wolfson, H. J.; Nussino, R. Studies of protein-protein interfaces:a statistical analysis of the hydrophobic effect. Protein Sci.1997,6, 53-64.
60. Akahane, K.; Nagano, Y.; Umeyama, H. Hydrophobic effect on the protein-ligand interaction; hydrophobic field-effect index and hydrophobic correlation index. Chem. Pharm. Bull.1989,37,86-92.
61. Spyrakis, F.; Cozzini, P.; Bertoli, C.; Marabotti, A.; Kellogg, G. E.; Mozzarelli, A. Energetics of the protein-DNA-water interaction. BMC Struct. Biol.2007,7, 4.
62. Buckingham, A. D.; Fowler, P. W.; Hutson, J. M. Theoretical studies of van der Waals molecules and intermolecular forces. Chem. Rev.1988,88,963-988.
63. Roth, C. M.; Neal, B. L.; Lenhoff, A. M. van der Waals interactions involving proteins. Biophys. J.1996,70,977-987.
64. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz Jr, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules.J. Am. Chem. Soc.1995,117,5179-5197.
65. Ott, K.-H.; Meyer, B. Parametrization of GROMOS force field for oligosaccharides and assessment of efficiency of molecular dynamics simulations.J. Comput. Chem.1996,17,1068-1084.
66. Morris, G. M.; Goodsell, D. S. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998,19,1639-1662.
67. Verdonk, M. L.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Taylor, R. D. Improved protein-ligand docking using GOLD. Proteins 2003,52,609-623.
68. Honig, B.; Nicholls, A. Classical electrostatics in biology and chemistry. Science 1995,268,1144-1149.
69. Fogolari, F.; Brigo, A.; Molinari, H. The Poisson-Boltzmann equation for biomolecular electrostatics:a tool for structural biology. J. Mol. Recognit.2002, 15,377-392.
70. Rocchia, W.; Alexov, E.; Honig, B. Extending the applicability of the nonlinear Poisson-Boltzmann equation:multiple dielectric constants and multivalent ions. J. Phys. Chem. B 2001,105,6507-6514.
71. McCoy, A. J.; Chandana, V.; Colman, P. M. Electrostatic complementarity at protein/protein interfaces.J. Mol. Biol.1997,268,570-584.
72. Ledvina, P. S.; Yao, N.; Choudhary, A.; Quiocho, F. A. Negative electrostatic surface potential of protein sites specific for anionic ligands. Proc. Natl. Acad. Sci. USA 1996,93,6786-6791.
73. Norberg, J. Association of protein-DNA recognition complexes:electrostatic and nonelectrostatic effects. Arch. Biochem. Biophys.2003,410,48-68.
74. D'Aquino, J.A.; Gomez, J.; Hilser, V. J.; Lee, K. H.; Amzel, L. M.; Fieire, E. The magnitude of the backbone conformational entropy change in protein folding. Proteins 1996,25,143-156.
75. Koehl, P.; Delarue, M. Application of a self-consistent mean field theory to predict protein side-chains conformation and estimate their conformational entropy. J. Mol. Biol.1994,239,249-275.
76. Zhang, J.; Liu, J. S. On side-chain conformational entropy of proteins. PLoS Comput. Biol.2006,2, e168.
77. Karplus, M.; Lchiye, T.; Pettitt, B. M. Configurational entropy of native proteins. Biophys. J.1987,52,1083-1085.
78. Doig, A. J.; Sternberg, M. J. E. Side-chain conformational entropy in protein folding. Protein Sci.1995,4,2247-2251.
79. Fischer, S.; Verma, C. S. Binding of buried structural water increases the flexibility of proteins. Proc. Natl. Acad. Sci. USA 1999,96,9613-9615.
80. Fischer, S.; Smith, J. C.; Verma, C. S. Dissecting the vibrational entropy change on protein/ligand binding:burial of a water molecule in bovine pancreatic trypsin inhibitor. J. Phys. Chem. B 2001,105,8050-8055.
81. McMahon, T. B.; Kebarle, P. Strong hydrogen bonding in gas-phase ions:a high-pressure mass-spectrometric study of formation and energetics of methyl fluoride proton-bound dimmer. J. Am. Chem. Soc.1986,108,6502-6505.
82. Legon, A. C.; Millen, D. A. Directional character, strength,. and nature of the hydrogen bond in gas-phase dimmers. Acc. Chem. Res.1987,20,39-46.
83. Iqbal, M.; Balaram, P. The 310 helical conformation of the amino terminal decapeptide of suzukacillin.270 MHz hydrogen-1 NMR evidence for eight intramolecular hydrogen bonds. J. Am. Chem. Soc.1981,103,5548-5552.
84. Menard, R.; Plouffe, C.; Khouri, H. E.; Dupras, R.; Tessier, D. C; Vernet, T. Thomas, D. Y.; Storer, A. C. Removal of an inter-domain hydrogen bond through site-directed mutagenesis:role of serine 176 in the mechanism of papain. Protein Eng.1991,4,307-311.
85. Sun, D. P.; Sauer, U.; Nicholson, H.; Matthews, B. W. Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. Biochemistry 1991,30,7142-7153.
86. Barratt, E.; Bingham, R. J.; Warner, D. J.; Laughton, C. A.; Phillips, S. E. V.; Homans, S. W. van der Waals interactions dominate ligand-protein association in a protein binding site occluded from solvent water. J. Am. Chem. Soc.2005, 127,11827-11834.
87. Ramanadham, M.; Jakkal, V. S.; Chidambaram, R. Carboxyl group hydrogen bonding in X-ray protein structures analysed using neutron studies on amino acids. FEBS Lett.1993,323,203-206.
88. Chatake, T.; Higuchi, Y.; Mizuno, N.; Tanak, I.; Niimura, N.; Morimotoa, Y. Hydrogen bonds of DsrD protein revealed by neutron crystallography. J. Synchrotron Radiat. 2008,15,277-280.
89. Alexandrescu, A. T.; Snyder, D. R.; Abildgaard, F. NMR of hydrogen bonding in cold-shock protein A and an analysis of the influence of crystallographic resolution on comparisons of hydrogen bond lengths. Protein Sci.2001,10, 1856-1868.
90. Bartlett, R. J.; Schweigert, I. V.; Lotrich, V. F. Ab initio DFT:getting the right answer for the right reason. J. Mol. Struct. (Theochem) 2006,771,1-8.
91.林梦海.量子化学计算方法与应用；科学出版社：北京,2004.
92. Lill, S. O. N. Application of dispersion-corrected density functional theory. J. Phys. Chem. A 2009,113,10321-10326.
93. Foster, J. P.; Weinhold, F. Natural atomic orbitals and natural population analysis. J. Am. Chem. Soc.1980,102,7211-7218.
94. Bader, R. F. W. Atoms in Molecules:A Quantum Theory; Oxford University Press:UK,1990.
95. Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J. Chem. Theory Comput.2006,2, 815-826.
96. Senthilkumar, K.; Mujika, J. I.; Ranaghan, K. E.; Manby, F. R.; Mulholland, A. J.; Harvey, J. N. Analysis of polarization in QM/MM modelling of biologically relevant hydrogen bonds. J. R. Soc. Interface 2008,5,207-216.
97. Lu, S.-Y.; Jiang, Y.-J.; Zhou, P.; Zou, J.-W.; Wu, T.-X. Geometric characteristics and energy landscapes of halogen-water-hydrogen bridges at protein-ligand interfaces. Chem. Phys. Lett.2010,485,348-353.
98. Sundaresan, N.; Pillai, C. K. S.; Suresh, C. H. Role of Mg2+ and Ca2+ in DNA bending:evidence from an ONIOM-based QM-MM study of a DNA fragment. J. Phys. Chem. A 2006,110,8826-8831.
99. Guallar, V.; Wallrapp, F. Mapping protein electron transfer pathways with QM/MM methods. J. R. Soc. Interface 2008,5, S233-S239.
100. Goedecker, S. Linear scaling electronic structure methods. Rev. Mod. Phys. 1999,71,1085-1123.
101. Cole, D. J.; Skylaris, C.-K.; Rajendra, E.; Venkitaraman, A. R.; Payne M. C. Protein-protein interactions from linear-scaling first-principles quantum-mechanical calculations. Europhys. Lett.2010,91,37004.
102. Muzet, N.; Guillot, B.; Jelsch, C.; Howard, E.; Lecomte, C. Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations. Proc. Natl. Acad. Sci. USA 2003,100,8742-8747.
103. MacKerell Jr, A. D.; Bashford, D.; Bellott, M.; Dunbrack Jr, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy,'D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher Ⅲ, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 1998,102,3586-3616.
104. Jorgensen, W. J.; Maxwell, D. S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc.1996,118,11225-11236.
105. Adcock, S. A.; McCammon, J. A. Molecular dynamics:survey of methods for simulating the activity of proteins. Chem. Rev.2006,106,1589-1615.
106. Kendrew, J. C.; Bodo, G.; Dintzis, H. M.; Parrish, R. G.; Wyckoff, H.; Phillips, D. C. A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 1958,181,662-666.
107. Berman H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
108. Hermans, J. Hydrogen bonds in molecular mechanics force fields. Adv. Protein Chem.2005,72,105-119.
109. Miyazawa, S.; Jernigan, R. L. Estimation of effective interresidue contact energies from protein crystal-structures—quasi-chemical approximation. Macromolecules 1985,18,534-552.
110. Grochowski, P.; Trylska, J. Continuum molecular electrostatics, salt effects, and counterion binding—a review of the Poisson-Boltzmann theory and its modifications. Biopolymers 2008,89,93-113.
111. Jain, A. N. Scoring functions for protein-ligand docking. Curr. Protein Pept. Sci.2006,7,407-420.
112. Zhou, P.; Tian, F.; Lv, F.; Shang, Z. Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins. Proteins 2009,76,151-163.
113. Zhou, P.; Zou, J.; Tian, F.; Shang, Z. Fluorine bonding—how does it work in protein-ligand interactions? J. Chem. Inf. Model.2009,49,2344-2355.
114. Zhou, P.; Lv, J.; Zou, J.; Tian, F.; Shang, Z. Halogen-water-hydrogen bridges in biomolecules. J. Struct. Biol.2010,169,172-182.
115. Zhou, P.; Ren, Y.; Tian, F.; Zou, J.; Shang, Z. Halogen-ionic bridges:do they exist in the biomolecular world? J. Chem. Theory Comput.2010,6,2225-2241.
116. Zhou, P.; Tian, F.; Zou, J.; Ren, Y.; Liu, X.; Shang, Z. Do halide motifs stabilize protein architecture? J. Phys. Chem. B 2010,114,15673-15686.
117. Zhou, P.; Tian, F.; Shang, Z.2D depiction of nonbonding interactions for protein complexes. J. Comput. Chem.2009,30,940-951.
118. Richardson, D. C. The Top500 Database; Kinemages Lab, Duke University:NC, USA.
119. Iwaoka, M.; Komatsu, H.; Katsuda, T.; Tomoda, S. Quantitative evaluation of weak nonbonded Se…F interactions and their remarkable nature as orbital interactions. J. Am. Chem. Soc.2002,124,1902-1909.
120. Matta, C. F.; Castillo, N.; Boyd, R. J. Characterization of a closedshell fluorine-fluorine bonding interaction in aromatic compounds on the basis of the electron density. J. Phys. Chem. A 2005,109,3669-3681.
121. Olsen, J. A.; Banner, D. W.; Seiler, P.; Sander, U. O.; D'Arcy, A.; Stihle, M.; Muller, K.; Diederich, F. A fluorine scan of thrombin inhibitors to map the fluorophilicity/fluorophobicity of an enzyme active site:evidence for C-F…C=O interactions. Angew. Chem., Int. Ed.2003,42,2507-2511.
122. Plenio, H. The Coordination chemistry of fluorine in fluorocarbons. ChemBioChem 2004,5,650-655.
123. Carosati, E.; Sciabola, S.; Crucia, G. Hydrogen bonding interactions of covalently bonded fluorine atoms:from crystallographic data to a new angular function in the GRID force field. J. Med Chem.2004,47,5114-5125.
124. Lu, Y.; Zou, J.; Yu, Q.; Jiang, Y.; Zhao, W. Ab initio investigation of halogen bonding interactions involving fluorine as an electron acceptor. Chem. Phys. Lett.2007,449,6-10.
125. Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals:looking beyond intuition. Science 2007,317,1881-1886.
126. Jeschke, P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem 2004,5,570-589.
127. Meyer, E. Internal water molecules and H-bonding in biological macromolecules:a review of structural features with functional implications. Protein Sci.1992,1,1543-1562.
128. Harding, M. M. The architecture of metal coordination groups in proteins. Acta Cryst.2004, D60,849-859.
129. Zhou, P.; Shang, Z.2D molecular graphics:a flattened world of chemistry and biology. Brief. Bioinform.2009,10,247-258.
1. Zhou, P.; Tian, F.; Lv, F.; Shang, Z. Geometric characteristics of hydrogen bonds involving sulfur atoms in proteins. Proteins 2009,76,151-163.
2. Jeffrey, G. A.; Saenger, W. Hydrogen Bonding in Biological Structures; Springer-Verlag:Berlin,1991.
3. Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond in Structural Chemistry and Biology; Oxford University Press:New York,1999.
4. Jiang, L.; Lai, L. C-H…O hydrogen bonds at protein-protein interfaces. J. Biol. Chem.2002,277,37732-37740.
5. Carosati, E.; Sciabola, S.; Cruciani, G. Hydrogen bonding interactions of covalently bonded fluorine atoms:from crystallographic data to a new angular function in the GRID force field. J. Med. Chem.2004,47,5114-5125.
6. Brandl, M.; Weiss, M. S.; Jabs, A.; Suhnel, J.; Hilgenfeld, R. C-H…p interactions in proteins. J. Mol. Biol.2001,307,357-377.
7. Scheiner, S. Hydrogen Bonding. A Theoretical Perspective; Oxford University Press:New York,1997.
8. Gilli, G.; Gilli, P. Towards an unified hydrogen-bond theory. J. Mol. Struct. 2000,552,1-15.
9. Pimentel, G. C.; Mcclellan, A. L. The Hydrogen Bond; Freeman:San Franciso, 1960.
10. Sabin, J. R. Hydrogen bonds involving sulfur. Ⅰ. The hydrogen sulfide dimer. J. Am. Chem. Soc.1971,93,3613-3620.
11. Sabin, J. R. Hydrogen bonds involving sulfur. Ⅱ. The hydrogen sulfide-hydrosulfide complex. J. Chem. Phys.1971,54,4675-4680.
12. Platts, J. A.; Howard, S. T.; Bracke, B. R. F. Directionality of hydrogen bonds to sulfur and oxygen. J. Am. Chem. Soc.1996,118,2726-2733.
13. Wennmohs, F.; Staemmler, V.; Schindler, M. Theoretical investigation of weak hydrogen bonds to sulfur. J. Chem. Phys.2003,119,3208-3218.
14. Allen, F. H.; Bird, C. M.; Rowland, R. S.; Raithby, P. R. Hydrogen-bond acceptor and donor properties of divalent sulfur (Y-S-Z and R-S-H). Acta Cryst.1997,B53,696-701.
15. Steiner, T. S-H…S hydrogen-bond chain in thiosalicylic acid. Acta Cryst.2000, C56,876-877.
16. Krepps, M. K.; Parkin, S.; Atwood, D. A. Hydrogen bonding with sulfur. Cryst. Growth Des.2001,1,291-297.
17. Tsunehiko, H.; Noriyuki, S.; Tetsuo, N. Effect of hydrogen bond toward the sulfur atom on electron transfer activity of metal-sulfur complexes. Sanka Hanno Toronkai Koen Yoshishu 2001,34,97-99.
18. Kamphuis, I. G.; Drenth, J.; Baker, E. N. Thiol proteases. Comparative studies based on the high-resolution structures of papain and actinidin, and on amino acid sequence information for cathepsins B and H, and stem bromelain. J. Mol. Biol.1985,182,317-329.
19. Bazan, J. F.; Fletterick, R. J. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases:structural and functional implications. Proc. Natl. Acad. Sci. USA 1988,85,7872-7876.
20. Beck, B. W.; Xie, Q.; Ichiye, T. Sequence determination of reduction potentials by cysteinyl hydrogen bonds and peptide dipoles in [4Fe-4S] ferredoxins. Biophys. J.2001,81,601-613.
21. Gregoret, L. M.; Rader, S. D.; Fletterick, R. J.; Cohen, F. E. Hydrogen bonds involving sulfur atoms in proteins. Proteins 1991,9,99-107.
22. Rajagopal, S.; Vishveshwara, S. Short hydrogen bonds in proteins. FEBS J. 2005,272,1819-1832.
23. Panigrahi, S. K.; Desiraju, G. R. Strong and weak hydrogen bonds in the protein-ligand interface. Proteins 2007,67,128-141.
24. Pal, D.; Chakrabarti, P. Non-hydrogen bond interactions involving the methionine sulfur atom. J. Biomol. Struct. Dyn.2001,19,115-128.
25. Richardson, D. C. The Top500 Database; Kinemages Lab, Duke University:NC, USA.
26. Word, J. M.; Lovell, S. C.; LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol.1999,285,1711-1733.
27. Engh, R. A.; Huber, R. Accurate bond and angle parameters for X-ray protein structure refinement. Acta Cryst.1991, A47,392-400.
28. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
29. Brunger, A. T.; Karplus, M. Polar hydrogen positions in proteins:empirical energy placement and neutron diffraction comparison. Proteins 1988,4, 148-156.
30. Forrest, L. R.; Honig, B. An assessment of the accuracy of methods for predicting hydrogen positions in protein structures. Proteins 2005,61,296-309.
31. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins. J. Mol. Biol.1994,238,777-793.
32. Steiner, T.; Koellner, G. Hydrogen bonds with p-acceptors in proteins: frequencies and role in stabilizing local 3D structures. J. Mol. Biol.2001,305, 535-557.
33. Viswanathan, R.; Dyke, T. R. The structure of H2S…HF and the stereochemistry of the hydrogen bond. J. Chem.Phys.1982,77,1166-1174.
34. Willoughby, L. C.; Fillery-Travis, A. J.; Legon, A. C. An investigation of the rotational spectrum of H2S…HF by pulsed-nozzle, Fourier-transform microwave spectroscopy:determination of the hyperfine coupling constants χaa(33S), χaaD, and DaaH(D)F. J. Chem. Phys.1984,81,20-26.
35. Legon, A. C.; Millen, D. A. Directional character, strength, and nature of the hydrogen bond in gas-phase dimers. Acc. Chem. Res.1987,20,39-46.
36. Gray, T. M.; Matthews, B. W. Intrahelical hydrogen bonding of serine, threonine, and cysteine residues within a-helices and its relevance to membrane-bound proteins. J. Mol. Biol.1984,175,75-81.
37. Thornton, J. M. Disulphide bridges in globular proteins. J. Mol. Biol.1981,151, 261-287.
1. Zhou, P.; Zou, J.; Tian, F.; Shang, Z. Fluorine bonding—how does it work in protein-ligand interactions? J. Chem. Inf. Model.2009,49,2344-2355.
2. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based on recognition processes:a world parallel to hydrogen bonding. Acc. Chem. Res. 2005,38,386-395.
3. Dunitz, J. D.; Taylor, R. Organic fluorine hardly ever accepts hydrogen bonds. Chem. Eur. J.1997,3,89-98.
4. Alkortaa, I.; Rozasa, I.; Elgueroa, J.; Foces-Foces, C.; Canob, F. H. A statistical survey of the Cambridge structural database concerning density and packing. J. Mol. Struct.1996,382,205-213.
5. Ahuja, R.; Samuelson, A. G. Nonbonding interactions of anions with nitrogen heterocycles and phenyl rings:a critical Cambridge structural database analysis. CrystEngComm 2003,5,395-399.
6. Awwadi, F. F.; Willett, R. D.; Peterson, K. A.; Twamley, B. The nature of halogen…halogen synthons:crystallographic and theoretical studies. Chem. Eur. J.2006,12,8952-8960.
7. Kawahara, S.; Tsuzuki, S.; Uchimaru, T. Theoretical study of the C-F/p interaction:attractive tnteraction between fluorinated alkane and an electron-deficient p-system. J. Phys. Chem. A 2004,108,6744-6749.
8. Riley, K. E.; Merz, K. M. Effects of fluorine substitution on the edge-to-face interaction of the benzene dimer. J. Phys. Chem. B 2005,109, 17752-17756.
9. Chopra, D.; Nagarajan, K.; Row, T. N. G. Analysis of weak interactions involving organic fluorine:insights from packing features in substituted 4-keto-tetrahydroindoles. J. Mol. Struct.2008,888:70-83.
10. Vishnumurthy, K.; Row, T. N.; Venkatesan, K. Fluorine in crystal engineering: photodimerization of (1E,3E)-1-phenyl-4-pentafluorophenylbuta-1,3-dienes in the crystalline state. Photochem. Photobiol. Sci.2002,1,427-430.
11. Jackel, C.; Koksch, B. Fluorine in peptide design and protein engineering. Eur. J. Org. Chem.2005,21,4483-4503.
12. Borisenko, K. B.; Broschag, M.; Hargittai, I.; Klapo"tke, T. M.; Schroder, D.; Schulz, A.; Schwarz, H.; Tornieporth-Oetting, I. C.; White, P. S. Preparation of N(SeCl)2+X-(X=SbCl6 or FeCl4), F3CCSeNSeCCF3+SbCl6-, F3CCSeNSeCCF3, F3CCSeNSeCCF3 and F3CCSeSeC(CF3)C(CF3)SeSeCCF3. Electron diffraction study of F3CCSeSeCCF3 and crystal structure of the eight-membered heterocycle F3CCSeSeC(CF3)C(CF3)SeSeCCF3. J. Chem. Soc., Dalton Trans. 1994,2705-2712.
13. Iwaoka, M.; Komatsu, H.; Katsuda, T.; Tomoda, S. Quantitative evaluation of weak nonbonded Se…F interactions and their remarkable nature as orbital interactions. J. Am. Chem. Soc.2002,124,1902-1909.
14. Matta, C. F.; Castillo, N.; Boyd, R. J. Characterization of a closed-shell fluorine-fluorine bonding interaction in aromatic compounds on the basis of the electron density. J. Phys. Chem. A 2005,109,3669-3681.
15. Lee, S.; Mallik, A. B.; Fredrickson, D. C. Dipolar-dipolar interactions and the crystal packing of nitriles, ketones, aldehdyes, and C(sp2)-F groups. Cryst. Growth Des.2004,4,279-290.
16. Olsen, J. A.; Banner, D. W.; Seiler, P.; Sander, U. O.; D'Arcy, A.; Stihle, M.; Muller, K.; Diederich, F. A fluorine scan of thrombin inhibitors to map the fluorophilicity/fluorophobicity of an enzyme active site:evidence for C-F-C=O interactions. Angew. Chem. Int. Ed.2003,42,2507-2511.
17. Plenio, H. The Coordination chemistry of fluorine in fluorocarbons. ChemBioChem 2004,5,650-655.
18. Lu, Y.; Zou, J.; Yu, Q.; Jiang, Y.; Zhao, W. Ab initio investigation of halogen bonding interactions involving fluorine as an electron acceptor. Chem. Phys. Lett.2007,449,6-10.
19. Kovacs, A.; Varga, Z. Halogen acceptors in hydrogen bonding. Coord. Chem. Rev.2006,250,710-727.
20. Bettinger, H. F. How good is fluorine as a hydrogen-bond acceptor in fluorinated single-walled carbon nanotubes? ChemPhysChem 2005,6, 1169-1174.
21. Parsch, J.; Engels, J. W. C-F…H-C hydrogen bonds in ribonucleic acids. J. Am. Chem. Soc.2002,124,5664-5672.
22. Carosati, E.; Sciabola, S.; Crucia, G. Hydrogen bonding interactions of covalently bonded fluorine atoms:from crystallographic data to a new angular function in the GRID force field. J. Med. Chem.2004,47,5114-5125.
23. Bohm, H.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Muller, Obst-Sander, U.; Stahl, M. Fluorine in medicinal chemistry. ChemBioChem 2004,5,637-643.
24. Gerebtzoff, G.; Li-Blatter, X.; Fischer, H.; Frentzel, A.; Seelig, A. Halogenation of drugs enhances membrane binding and permeation. ChemBioChem 2004,5, 676-684.
25. Muller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals:looking beyond intuition. Science 2007,317,1881-1886.
26. Jeschke, P. The unique role of fluorine in the design of active ingredients for modern crop protection. ChemBioChem 2004,5,570-589.
27. Paulini, R.; Muller, K.; Diederich, F. Orthogonal multipolar interactions in structural chemistry and biology. Angew. Chem. Int. Ed.2005,44,1788-1805.
28. Kim, C.; Chandra, P. P.; Jain, A.; Christianson, D. W. Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the crystal lattice of human carbonic anhydrase Ⅱ. J. Am. Chem. Soc.2001,123, 9620-9627.
29. Shin, J.; Cho, D. PDB-Ligand:a ligand database based on PDB for the automated and customized classification of ligand-binding structures. Nucleic Acids Res.2005,33, D238-D241.
30. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
31. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl. Acad. Sci. USA 2004,101,16789-16794.
32. Krivov, G. G.; Shapovalov, M. V.; Dunbrack Jr, R. L. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 2009,77,778-795.
33. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
34. Bondi, A. van der Waals volumes and radii. J. Phys. Chem.1964,68,441-451.
35. Moller, C.; Plesset, M. S. Note on an approximation treatment for many-electron systems. Phys. Rev.1934,46,618-622.
36. Dunning Jr, T. H. The atoms boron through neon and hydrogen. J. Chem. Phys. 1989,90,1007-1023.
37. Sahu, P. K.; Lee, S. Hydrogen-bond interactions in THF-H2O-HF:a theoretical study. Int. J. Quantum. Chem.2007,107,2015-2023.
38. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor. Chim. Acta.1969,13,230-248.
39. Boys, S.F.; Bernardi,F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
40. Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM.J. Chem. Theory Comput.2006,2, 815-826.
41. Adamo, C.; Barone, V. Exchange functionals with improved longrange behavior and adiabatic connection methods without adjustable parameters:the mPW and mPWIPW models. J. Chem. Phys.1998,108,664-675.
42. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, Jr., K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc.1995,117,5179-5197.
43. Lu,Y.;Shi,T.;Wang,Y.;Yang H.;Yan,X.;Luo,X.;Jiang,H.;Zhu,W. Halogen bonding--a novel interaction for rational drug design?J.Med.Chem. 2009,52,2854-2862.
44. Jorgensen,W.L.；Chandrasekhar,J.;Madura,J.D.Impey,R.W.;Klein, M.L.； Comparison of simple potential functions for simulating liquid water,J.Chem. Phys.1983,79,926-935.
45. Comell,W.D.;Cieplak,P.;Bayly,C.I.;Kollman,P.A.Application of RESP charges to calculate conformational energies,hydrogen bond energies,and free energies of solvation.J.Am.Chem.Soc.1993,115,9620-9631.
46. Wang,J.;Wolf, R.M.;Caldwell,J.W.;Kollman,P.A.;Case,D.A.Developing and testing of a general amber force field.J.Comput.Chem.2004,25, 1157-1174.
47. Alzate-Morales,J.H.;Caballero,J.；Jague,A.V.;Nilo,F.D.G. Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2(CDK2)inhibitors:prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculation.J.Chem.Inf. Mode.2009,49,886-899.
48. Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G. E.;Robb,M.A.; Cheeseman,J.R.;Zakrzewski,V G.;Montgomery,J.A.;Stratmann,R.E.; Burant,J.C.;Dapprich,S.;Millam,J.M.;Daniels,A.D.;Kudin,K.N.;Strain, M.C.;Farkas,O.;Tomasi,J.;Barone,V.;Cossi,M.;Cammi,R.；Mennucci,B.； Pomelli,C.;Adamo,C.;Clifford,S.;Ochterski,J.;Petersson,G. A.;Ayala,P.Y.; Cui,Q.；Morokuma,K.；Malick,D.K.;Rabuck,A.D.；Raghavachari,K. Foresman,J.B.;Cioslowski,J.;Ortiz,J.V.;Stefanov,B.B.;Liu,G.;Liashenko, A.；Piskorz,P.;Komaromi,I.;Gomperts,R.;Martin,R.L.;Fox,D.J.;Keith,T.; Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Gonzalez,C.;Challacombe, M.；Gill,P.M.W.;Johnson,B.G.;Chen,W.;Wong,M.W.;Andres,J.L. Head-Gordon,M.;Replogle,E.S.；Pople,J.A.Gaussian 03；Gaussian,Inc., Wallingford,CT,USA,2003.
49. Ponder, J. W.; Richards, F. M. An efficient newton-like method for molecular mechanics energy minimization of large molecules. J. Comput. Chem.1987,8, 1016-1024.
50. HyperChem, version 8.0; Hypercube Inc., Gainesville, FL, USA,2009.
51. Discovery Studio, version 2.1; Accelrys Inc., San Diego, CA, USA,2008.
52. Olsen, J. A.; Banner, D. W.; Seiler, P.; Wagner, B.; Tschopp, T.; Obst-Sander, U.; Kansy, M.; Muller, K.; Diederich, F. Fluorine interactions at the thrombin active site:protein backbone fragments H-Ca-C=O comprise a favorable C-F environment and Interactions of C-F with electrophiles. ChemBioChem 2004,5, 666-675.
53. Fields, B. A.; Bartsch, H. H.; Bartunik, H. D.; Cordes, F.; Guss, J. M.; Freeman, H. C. Accuracy and precision in protein crystal structure analysis:two independent refinements of the structure of poplar plastocyanin at 173 K. Acta Cryst.1994, D50,709-730.
54. Morozov, A. V.; Kortemme, T.; Tsemekhman, K.; Baker, D. Close agreement between the orientation dependence of hydrogen bonds observed in protein structures and quantum mechanical calculations. Proc. Natl. Acad. Sci. USA 2004,101,6946-6951.
55. DiMagno, S.; Sun, H. The strength of weak interactions:aromatic fluorine in drug design. Curr Top. Med. Chem.2006,6,1473-1482.
56. Feyereisen, M. W.; Feller, D.; Dixon, D. A. Hydrogen bond energy of the water dimer. J. Phys. Chem.1996,100,2993-2997.
57. Taylor, R.; Kennard, O.; Versichel, W. Geometry of the N-H…O=C hydrogen bond.1. Lone-pair directionality. J. Am. Chem. Soc.1983,105,5761-5766.
58. Isaacs, E. D.; Shukla, A.; Platzman, P. M.; Hamann, D. R.; Barbiellini, B.; Tulk, C. A. Covalency of the hydrogen bond in ice:a direct X-ray measurement. Phys. Rev. Lett.1999,82,600-603.
59. Obst, U.; Gramlich, V.; Diederich, F.; Weber, L.; Banner, D. W. Design of novel, nonpeptidic thrombin inhibitors and structure of a thrombin-inhibitor complex. Angew. Chem. Int. Ed.1995,34,1739-1742.
60. Obst, U.; Banner, D. W.; Weber, L.; Diederich, F. Molecular recognition at the thrombin active site:structure-based design and synthesis of potent and selective thrombin inhibitors and the X-ray crystal structures of two thrombin-inhibitor complexes. Chem. Biol.1997,4,287-295.
61. Hof, F.; Scofield, D. M.; Schweizer, W. B.; Diederich, F. A weak attractive interaction between organic fluorine and an amide group. Angew. Chem. Int. Ed. 2004,43,5056-5059.
62. Foster, J. P.; Weinhold, F. Natural atomic orbitals and natural population analysis. J. Am. Chem. Soc.1980,102,7211-7218.
63. Lu, Y.; Zou, J.; Fan, J.; Zhao, W.; Jiang, Y.; Yu, Q. Ab initio calculations on halogen-bonded complexes and comparison with density functional methods.J. Comput. Chem.2009,30,725-732.
64. Peterson, S. A.; Klabunde, T.; Lashuel, H. A.; Purkey, H.; Sacchettini, J. C.; Kelly, J. W. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc. Natl. Acad. Sci. USA 1998,95,12956-12960.
65. Kim, C.; Chang, J. S.; Doyon, J. B.; Baird, T. T.; Fierke, C. A.; Jain, A.; Christianson, D. W. Contribution of fluorine to protein-ligand affinity in the binding of fluoroaromatic inhibitors to carbonic anhydrase Ⅱ. J. Am. Chem. Soc. 2000,122,12125-12134.
66. Sorme, P.; Arnoux, P.; Kahl-Knutsson, B.; Leffler, H.; Rini, J. M.; Nilsson, U. J. Structural and thermodynamic studies on cation-p interactions in lectin-ligand complexes:high-affinity galectin-3 inhibitors through fine-tuning of an arginine-arene interaction. J. Am. Chem. Soc.2005,127,1737-1743.
67. Benson, M. L.; Smith, R. D.; Khazanov, N. A.; Dimcheff, B.; Beaver, J.; Dresslar, P.; Nerothin, J.; Carlson, H. A. Binding MOAD, a high-quality protein-ligand database. Nucleic Acids Res.2008,36, D674-D678.
1. Zhou, P.; Lv, J.; Zou, J.; Tian, F.; Shang, Z. Halogen-water-hydrogen bridges in biomolecules. J. Struct. Biol.2010,169,172-182.
2. Levy, Y.; Onuchic, J. N. Water and proteins:a love-hate relationship. Proc. Natl. Acad. Sci. USA 2004,101,3325-3326.
3. Williams, M. A.; Goodfellow, J. M.; Thornton, J. M. Buried waters and internal cavities in monomeric proteins. Protein Sci.1994,3,1224-1235.
4. Janin, J. Wet and dry interfaces:the role of solvent in protein-protein and protein-DNA recognition. Struct. Fold. Des.1999,7, R277-279.
5. Covell, D. G.; Wallqvist, A. Analysis of protein-protein interactions and the effects of amino acid mutations on their energetics. The importance of water molecules in the binding epitope. J. Mol. Biol.1997,269,281-297.
6. Papoian, G. A.; Ulander, J.; Wolynes, P. G. Role of water mediated interactions in protein-protein recognition landscapes. J. Am. Chem. Soc.2003,125, 9170-9178.
7. Lunin, V. V.; Li, Y.; Schrag, J. D.; Iannuzzi, P.; Cygler, M.; Matte, A. Crystal structures of Escherichia coli ATP-dependent glucokinase and its complex with glucose. J. Bacteriol.2004,186,6915-6927.
8. Dreyer, G. B.; Lambert, D. M.; Meek, T. D.; Carr, T. J.; Tomaszek Jr, T. A.; Fernandez, A. V.; Bartus, H.; Cacciavillani, E.; Hassell, A. M. Hydroxyethylene isostere inhibitors of human immunodeficiency virus-1 protease: structure-activity analysis using enzyme kinetics, X-ray crystallography, and infected T-cell assays. Biochemistry 1992,31,6646-6659.
9. Helms, V.; Wade, R. C. Thermodynamics of water mediating protein-ligand interactions in cytochrome P450cam:a molecular dynamics study. Biophys. J. 1995,69,810-824.
10. Jiang, L.; Kuhlman, B.; Kortemme, T.; Baker, D. A "solvated rotamer" approach to modeling water-mediated hydrogen bonds at protein-protein interfaces. Proteins 2005,58,893-904.
11. Bui, H. H.; Schiewe, A. J.; Haworth, I. S. WATGEN:an algorithm for modeling water networks at protein-protein interfaces. J. Comput. Chem.2007,28, 2241-2251.
12. Goodfellow, J. M. Cooperative effects in water-biomolecule crystal systems. Proc. Natl. Acad. Sci. USA 1982,79,4977-4979.
13. Steinbach, P. J.; Brooks, B. R. Protein hydration elucidated by molecular dynamics simulation. Proc. Natl. Acad. Sci. USA 1993,90,9135-9139.
14. Meyer, E. Internal water molecules and hydrogen bonding in biological macromolecules:a review of structural features with functional implications. Protein Sci.1992,1,1543-1562.
15. Sun, Y.; Kollman, P. Are there water bridge-induced hydrophilic interactions. J. Phys. Chem.1996,100,6760-6763.
16. Sevilla, M. D.; Summerfield, S.; Eliezer, I.; Rak, J.; Symons M. C. R. Interaction of the chlorine atom with water:ESR and ab initio MO evidence for three-electron (s2s*1) bonding. J. Phys. Chem. A 1997,101,2910-2915.
17. Davey, J. B.; Legon, A. C. Rotational spectroscopy of the gas phase complex of water and bromine monochloride in the microwave region:geometry, binding strength and charge transfer. Phys. Chem. Chem. Phys.2001,3,3006-3011.
18. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl. Acad. Sci. USA 2004,101,16789-1679.
19. Metrangolo, P.; Resnati, G. Halogen versus hydrogen. Science 2008,321, 918-919.
20. Green, D. E.; Zande, H. D. V. Universal energy principle of biological systems and the unity of bioenergetics. Proc. Natl. Acad. Sci. USA 1981,78,5344-5347.
21. Metrangolo, P.; Neukirch, H.; Pilati, T.; Resnati, G. Halogen bonding based recognition processes:a world parallel to hydrogen bonding. Acc. Chem. Res. 2005,38,386-395.
22. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 03; Gaussian, Inc., Wallingford, CT, USA,2003.
23. Legon, A. C.; Thumwood, J. M. A. Properties of the halogen-bonded complex H2S…Br2 established by rotational spectroscopy and ab initio calculations. Phys. Chem. Chem. Phys.2001,3,2758-2764.
24. Legon, A. C.; Thumwood, J. M. A.; Waclawik, E. R. The interaction of water and dibromine in the gas phase:an investigation of the complex H2O…Br2 by rotational spectroscopy and ab initio calculations. Chem. Eur. J.2002,8, 940-950.
25. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor. Chim. Acta.1969,13,230-248.
26. Boys, S. F.; Bernardi, F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
27. Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J. Chem. Theory Comput.2006,2, 815-826.
28. Adamo, C.; Barone, V. Exchange functionals with improved longrange behavior and adiabatic connection methods without adjustable parameters:the mPW and mPWIPW models. J. Chem. Phys.1998,108,664-675.
29. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AM1:a new general-purpose quantum mechanical molecular model. J. Am. Chem. Soc.1985, 107,3902-3909.
30. Lu, Y.; Zou, J.; Fan, J.; Zhao, W.; Jiang, Y.; Yu, Q. Ab initio calculations on halogen-bonded complexes and comparison with density functional methods. J. Comput. Chem.2009,30,725-732.
31. Esseffar, M.; Bouab, W.; Lamsabhi, A.; Abboud, J. L. M.; Notario, R.; Yanez, M. An experimental and theoretical study on some thiocarbonyl-Ⅰ2 molecular complexes. J. Am. Chem. Soc.2000,122,2300-2308.
32. Lu, Y.; Zou, J.; Yu, Q.; Jiang, Y.; Zhao, W. Ab initio investigation of halogen bonding interactions involving fluorine as an electron acceptor. Chem. Phys. Lett.2007,449,6-10.
33. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins. J. Mol Biol.1994,238,777-793.
34. Steiner, T.; Koellner, G. Hydrogen bonds with p-acceptors in proteins: frequencies and role in stabilizing local 3D structures. J. Mol. Biol.2001,305, 535-557.
35. Lu, Y.; Zou, J.; Wang, Y.; Zhang, H.; Yu, Q.; Jiang, Y. A quantitative insight into the'amphiphilicity' of covalently-bonded halogens from ab initio calculations. J. Mol. Struct. (Theochem) 2006,766,119-124.
36. Bondi, A. van der Waals volumes and radii. J. Chem. Phys.1964,68,441-451.
37. Ouvrard, C.; Questel, J. Y. L.; Berthelot, M.; Laurence, C. Halogen-bond geometry:a crystallographic database investigation of dihalogen complexes. Acta. Cryst.2003, B59,512-526.
38. Kortagere, S.; Ekins, S.; Welsh, W. J. Halogenated ligands and their interactions with amino acids:implications for structure-activity and structure-toxicity relationships. J. Mol. Graph. Model.2008,27,170-177.
39. Feyereisen, M. W.; Feller, D.; Dixon, D. A. Hydrogen bond energy of the water dimer. J. Phys. Chem.1996,100,2993-2997.
40. Grabowski, S. J.; Bilewicz, E. Cooperativity halogen bonding effect—ab initio calculations on H2CO…(ClF)n complexes. Chem. Phys. Lett.2006,427,51-55.
41. Li, Q.; Lin, Q.; Li, W.; Cheng, J.; Gong, B.; Sun, J. Cooperativity between the halogen bond and the hydrogen bond in H3N…XY…HF complexes (X, Y=F, Cl, Br). ChemPhysChem 2008,9,2265-2269.
42. Foster, J. P.; Weinhold, F. Natural atomic orbitals and natural population analysis. J. Am. Chem. Soc.1980,102,7211-7218.
43. Rivelino R.; Rivelino R.; Chaudhuri, P.; Canuto, S. Quantifying multiple-body interaction terms in hydrogen-bonded HCN chains with many-body perturbation/coupled-cluster theories. J. Chem. Phys.2003,118,10593-10601.
44. Petukhov, M.; Cregut, D.; Soares, C. M.; Serrano, L. Local water bridges and protein conformational stability. Protein Sci.1999,8,1982-1989.
45. Word, J. M.; Lovell, S. C.; LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol.1999,285,1711-1733.
46. Lommerse, J. P. M.; Stone, A. J.; Taylor, R.; Allen, F. H. The nature and geometry of intermolecular interactions between halogens and oxygen or nitrogen. J. Am. Chem. Soc.1996,118,3108-3116.
47. Mahoney, M. W.; Jorgensen, W. L. A five-site model for liquid water and the reproduction of the density anomaly by rigid, nonpolarizable potential functions. J. Chem. Phys.2000,112,8910-8922.
48. Otting, G.; Liepinsh, E.; Wuthrich, K. Protein hydration in aqueous solution. Science 1991,254,974-980.
49. Ravelli, R. B. G.; Leiros, H. K. S.; Pan, B.; Caffrey, M. McSweeney, S. Specific radiation damage can be used to solve macromolecular crystal structures. Structure 2003,11,217-224.
50. Gerebtzoff, G.; Li-Blatter, X.; Fischer, H.; Frentzel, A.; Seelig, A. Halogenation of drugs enhances membrane binding and permeation. ChemBioChem 2004,5, 676-684.
51. Himmel, D. M.; Das, K.; Clark, A. D.; Hughes, S. H.; Benjahad, A.; Oumouch, S.; Guillemont, J.; Coupa, S.; Poncelet, A.; Csoka, I.; Meyer, C.; Andries, K.; Nguyen, C. H.; Grierson, D. S.; Arnold, E. Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives:a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains. J. Med. Chem.2005,48,7582-7591.
52. Jiang, Y.; Alcaraz, A. A.; Chen, J. M.; Kobayashi, H.; Lu, Y. J.; Snyder, J. P. Diastereomers of dibromo-7-epi-10-deacetylcephalomannine:crowded and cytotoxic taxanes exhibit halogen bonds. J. Med. Chem.2006,49,1891-1899.
53. Voth, A. R.; Ho, P. S. The role of halogen bonding in inhibitor recognition and binding by protein kinases. Curr. Top. Med. Chem.2007,7,1336-1348.
1. Zhou, P.; Ren, Y.; Tian, F.; Zou, J.; Shang, Z. Halogen-ionic bridges:do they exist in the biomolecular world? J. Chem. Theory Comput.2010,6,2225-2241.
2. Hofmeister, F. Zur Lehre von der Wirkung der Salze. Arch. Exp. Pathol. Pharmakol.1888,24,247-260.
3. Marcus, Y. Effect of ions on the structure of water:structure making and breaking. Chem. Rev.2009,109,1346-1370.
4. Zhang, Y.; Cremer, P. S. Interactions between macromolecules and ions:the Hofmeister series. Curr. Opin. Chem. Biol.2006,10,658-663, and references therein.
5. Takashima, K.; Riveros, J. M. Gas-phase solvated negative ions. Mass Spectrom. Rev.1998,17,409-430, and references therein.
6. Kovacs, A.; Varga, Z. Halogen acceptors in hydrogen bonding. Coord. Chem. Rev.2006,250,710-727, and references therein.
7. Arshadi, M.; Yamdagni, R.; Kebarle, P. Hydration of the halide negative ions in the gas phase. Ⅱ. Comparison of hydration energies for the alkali positive and halide negative ions. J. Phys. Chem.1970,74,1475-1482.
8. Caldwell, G.; Kebarle, P. Binding energies and structural effects in halide anion-ROH and-RCOOH complexes from gas-phase equilibria measurements. J. Am. Chem. Soc.1984,106,967-969.
9. Hiraoka, K.; Mizuse, S.; Yamabe, S. Solvation of halide ions with H2O and CH3CN in the gas phase. J. Phys. Chem.1988,92,3943-3957.
10. Bogdanov, B.; Peschke, M.; Tonner, D. S.; Szulejko, J. E.; McMahon, T. B. Stepwise solvation of halides by alcohol molecules in the gas phase. Int. J. Mass Spectrom.1999,187,707-725.
11. Klopper, W.; van Duijneveldt-van de Rijdt, J. G. C. M.; van Duijneveldt, F. B. Computational determination of equilibrium geometry and dissociation energy of the water dimer. Phys. Chem. Chem. Phys.2000,2,2227-2234.
12. Xantheas, S. S.; Dunning Jr, T.H. Structures and energetics of F-(H2O)n, n=1-3, clusters from ab initio calculations. J. Phys. Chem.1994,98,13489-13497.
13. Johnson, M. S.; Kuwata, K. T.; Wong, C. K.; Okumura, M. Vibrational spectrum of I- (H2O). Chem. Phys. Lett.1996,260,551-557.
14. Choi, J. H.; Kuwata, K.T.; Cao, Y. B.; Okumura, M. Vibrational spectroscopy of the Cl-(H2O)n anionic clusters, n=1-5. J. Phys. Chem. A 1998,102,503-507.
15. Kim, J.; Lee, H. M.; Suh, S. B.; Majumdar, D.; Kim, K. S. Comparative ab initio study of the structures, energetics and spectra of X-(H2O)n=1-4 [X=F, Cl, Br, I] clusters. J. Chem. Phys.2000,113,5259-5272.
16. Vinogradov, S. N. Hydrogen bonds in crystal structures of amino acids, peptides and related molecules. Int. J. Pept. Protein Res.1979,14,281-289.
17. Zhang, W.; Piculell, L.; Nilsson, S. Effects of specific anion binding on the helix-coil transition of lower charged carrageenans. NMR data and conformational equilibria analyzed within the Poisson-Boltzmann cell model. Macromolecules 1992,25,6165-6172.
18. Washabaugh, M. W.; Collins, K. D. The systematic characterization by aqueous column chromatography of solutes which affect protein stability. J. Biol. Chem. 1986,261,12477-12485.
19. Chen, X.; Yang, T.; Kataoka, S.; Cremer, P. S. Specific ion effects on interfacial water structure near macromolecules. J. Am. Chem. Soc.2007,129, 12272-12279.
20. Lund, M.; Vrbka, L.; Jungwirth, P. Specific ion binding to nonpolar surface patches of proteins. J. Am. Chem. Soc.2008,130,11582-11583.
21. Ninham, B. W.; Yaminsky, V. Ion binding and ion specificity:the Hofmeister effect and Onsager and Lifshitz theories. Langmuir 1997,13,2097-2108.
22. Lund. M.; Jungwirth, P.; Woodward, C. E. Ion specific protein assembly and hydrophobic surface forces. Phys. Rev. Lett.2008,100,258105.
23. Heyda, J.; Hrobarik, T.; Jungwirth, P. Ion-specific interactions between halides and basic amino acids in water. J. Phys. Chem. A 2009,113,1969-1975.
24. Meyer, E. Internal water molecules and hydrogen bonding in biological macromolecules:a review of structural features with functional implications. Protein Sci.1992,1,1543-1562.
25. Sun, Y., Kollman, P. Are there water bridge-induced hydrophilic interactions. J. Phys. Chem.1996,100,6760-6763.
26. Zhou, P.; Lv, J.; Zou, J.; Tian, F.; Shang, Z. Halogen-water-hydrogen bridges in biomolecules. J. Struct. Biol.2010,169,172-182.
27. Rutenber, E.; Fauman, E. B.; Keenan, R. J.; Fong, S.; Furth, P. S.; Ortiz de Montellano, P. R.; Meng, E.; Kuntz, I. D.; DeCampn, D. L.; Saltoll, R.; Rosb, J. R.; Craik, C. S.; Stroud, R. M. Structure of a non-peptide inhibitor complexed with HIV-1 protease. Developing a cycle of structure-based drug design. J. Biol. Chem.1993,268,15343-15346.
28. Moller, C.; Plesset, M. S. Note on an approximation treatment for many-electron systems. Phys. Rev.1934,46,618-622.
29. Bader, R. F. W. Atoms in Molecules:A Quantum Theory; Oxford University Press:UK,1990.
30. Reed, A. E.; Curitss, L. A.; Weinhold, F. Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem. Rev.1988,88,889-926.
31. Raghavachari, K.; Trucks, G. W.; Pople, J. A.; Head-Gordon, M. A. A fifth-order perturbation comparison of electron correlation theories. Chem. Phys. Lett.1989, 157,479-483.
32. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor., Chim. Acta.1969,13,230-248.
33. Boys, S. F.; Bernardi, F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
34. Glukhovtsev, M. N.; Pross, A.; Radom, L. Gas-phase identity SN2 reactions of halide anions with methyl halides:a high-level computational study. J. Am. Chem. Soc.1995,117,2024-2032.
35. Sanov, A.; Faeder, J.; Parson, R.; Lineberger, W. C. Spin-orbit coupling in I·CO2 and I·OCS van der Waals complexes:beyond the pseudo-diatomic approximation. Chem.Phys.Lett.1999,3,3,812-819.
36.Cioslowski, J.; Piskorz, P. Properties of atoms in molecules from valence-electron densities augmented with core-electron contributions.Chem. Phys.Lett. 1996,255,315—319.
37.Asaduzzaman,A.M.;Schreckenbach,G.Computational study of the ground state properties of iodine and polyiodide ions.Theor.Chem.Account 2009,122, 119-125.
38.Vreven,T.;Byun,K.S.;Komaromi,I.;Dapprich,S.;Montgomery,J.A.; Morokuma,K.;Frisch,M.J.Combining quantum mechanics methods with molecular mechanics methods in ONIOM.J.Chem.Theory Comput.2006,2, 815-826.
39.Cornell,W.D.;Cieplak,P.;Bayly,C.I.;Gould,I.R.；Merz,Jr,K.M.;Ferguson, D.M.；Spellmeyer,D.C.；Fox,T.;Caldwell,J.W.;Kollman,P.A.A second generation force field for the simulation of proteins,nucleic acids,and organic molecules.J.Am.Chem.Soc.1995,117,5179-5197.
40.Jorgensen,W.L.;Chandrasekhar,J.;Madura,J.D.;Impey,R.W.;Klein,M.L. Comparison of simple potential functions for simulating liquid water.J.Chem. Phys.1983,79,926-935.
41.Comell,W.D.;Cieplak,P.；Bayly,C.I.;Kollman,P.A.Application of RESP charges to calculate conformational energies,hydrogen bond energies,and free energies of solvation.J.Am.Chem.Soc.1993,115,9620-9631.
42.Wang,J.;Wolf,R.M.;Caldwell,J.W.;Kollman,P.A.;Case,D.A.Developing and testing of a general amber force field.Comput.Chem.2004,25, 1157-1174.
43.Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.; Cheeseman,J.R.;Zakrzewski,V.G.;Montgomery,J.A.,Jr.;Stratmann,R.E.; Burant,J.C.;Dapprich,S.;Millam,J.M.;Daniels,A.D.;Kudin,K.N.;Strain, M.C.;Farkas,O.;Tomasi,J.;Barone,V.;Cossi,M.;Cammi,R.;Mennucci,B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T. Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L. Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 03; Gaussian, Inc.: Wallingford, CT,2003.
44. Biegler-Konig, F.; Schoenbohm, J. AIM2000,2.0 ed.; Buro fur Innovative Software:Bielefeld, Germany,2002.
45. Glendening, E. D.; Badenhoop, J, K.; Reed, A. E.; Carpente, J. E.; Bohmann, J. A.; Morales, C. M.; Weinhold, F. NBO 5.0; Theoretical Chemistry Institute, University of Wisconsin:Madison, WI,2001.
46. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
47. Krivov, G. G.; Shapovalov, M. V.; Dunbrack Jr., R. L. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 2009,77,778-795.
48. Kabsch, W.; Sander, C. Dictionary of protein secondary structure:pattern recognition of hydrogen-bonded and geometricalal features. Biopolymers 1983, 22,2577-2637.
49. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
50. Bas, D. C.; Rogers, D. M.; Jensen, J. H. Very fast prediction and rationalization of pKa values for protein-ligand complexes. Proteins 2008,73,765-783.
51. Zhao, Y.; Cheng, T.; Wang, R. Automatic perception of organic molecules based on essential structural information. J. Chem. Inf. Model.2007,47,1379-1385.
52. Sanner, M. F.; Olson, A. J.; Spehner, J.-C. Reduced surface:an efficient way to compute molecular surfaces. Biopolymers 1996,38,305-320.
53. Rother, K.; Hildebrand, P. W.; Goede, A.; Gruening, B.; Preissner, R. Voronoia: analyzing packing in protein structures. Nucleic Acids Res.2009,37, D393-D935.
54. Tsai, J.; Taylor, R.; Chothia, C.; Gerstein, M. The packing density in proteins: standard radii and volumes. J. Mol. Biol.1999,290,253-266.
55. Shannon, R. D. Revised effective ionic radii and systematic studies of interatomic distances in halides and chaleogenides. Acta Cryst.1976, A32, 751-767.
56. Ooi, T.; Oobatake, M.; Nemethy, G.; Scheraga, H. A. Accessible surface areas as a measure of the thermodynamic parameters of hydration of peptides. Proc. Natl. Acad. Sci. USA 1987,84,3086-3090.
57. Klots, C. E. Solubility of protons in water. J. Phys. Chem.1981,85,3585-3588.
58. Meot-Ner, M. The ionic hydrogen bond. Chem. Rev.2005,105,213-284.
59. Nakanishi, W.; Hayashi, S.; Narahara, K. Atoms-in-molecules dual parameter analysis of weak to strong interactions:behaviors of electronic energy densities versus Laplacian of electron densities at bond critical points.J. Phys. Chem. A 2008,112,13593-13599.
60. Wiberg, K. B. Application of the pople-santry-segal CNDO method to the cyclopropylcarbinyl and eyelobutyl cation and to bicyelobutane. Tetrahedron 1968,24,1083-1096.
61. Reed, A. E.; Schleyer, P. The anomeric effect with central atoms other than carbon.2. Strong interactions between nonbonded substituents in mono-and polyfluorinated first- and second-row amines, FnAHmNH2. Inorg. Chem.1988,27, 3969-3987.
62. Chesnut D. B. A simple definition of ionic bond order. J. Chem. Theory Comput. 2008,4,1637-1642.
63. Prabakaran, P.; Singarayan, M. G. Long-range ordering in water-halide ion interactions:a database study. Chem. Lett.2004,33,1640-1641.
64. Rajagopal, S.; Vishveshwara, S. Short hydrogen bonds in proteins. FEBS J.2005, 272,1819-1832.
65. Auffinger, P.; Hays, F. A.; Westhof, E.; Ho, P. S. Halogen bonds in biological molecules. Proc. Natl. Acad. Sci. USA 2004,101,16789-16794.
66. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol. 1999,293,1241-1255.
67. Baldwin, R. L. Rose, G. D. Is protein folding hierarchic? Ⅱ. Folding intermediates and transition states. Trends Biochem. Sci.1999,24,77-84.
68. Tsai, C. J.; Xu, D.; Nussinov, R. Protein folding via binding and vice versa, Fold. Des.1998,3, R71-R80.
69. Lu, Y.; Wang, R.; Yang, C. Y.; Wang, S. Analysis of ligand-bound water molecules in high-resolution crystal structures of protein-ligand complexes. J. Chem. Inf. Model.2007,47,668-675.
70. Srinivasan, R.; Rose, G. D. A physical basis for protein secondary structure. Proc. Natl. Acad. Sci. USA 1999,96,14258-14263.
71. Lu, Y.; Shi, T.; Wang, Y.; Yang, H.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. Halogen bonding-a novel interaction for rational drug design. J. Med. Chem.2009,52, 2854-2862.
72. Lu, Y.; Wang, Y.; Xu, Z.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. C-X…H contacts in biomolecular systems:how they contribute to protein-ligand binding affinity. J. Phys. Chem. B 2009,113,12615-12621.
73. Alzate-Morales, J. H.; Caballero, J.; Jague, A. V.; Nilo, F. D. G. Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors:prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculation.J. Chem. Inf. Model.2009,49, 886-899.
74. Feldman, R. I.; Wu, J. M.; Polokoff, M. A. Kochanny, M. J.; Dinter, H.; Zhu, D.; Biroc, S. L.; Alicke, B.; Bryant, J.; Yuan, S.; Buckman, B. O.; Lentz, D.; Ferrer, M.; Whitlow, M.; Adler, M.; Finster, S.; Chang, Z.; Arnaiz, D. O. Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem. 2005,280,19867-19874.
75. Word, J. M.; Lovell, S. C.;, LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol.1999,285,1711-1733.
76. Zhou, P.; Tian, F.; Zou, J.; Shang Z. Rediscovery of halogen bonds in protein-ligand complexes. Mini Rev. Med. Chem.2010,10,309-314.
77. Bondi, A. van der Waals volumes and radii. J. Phys. Chem.1964,68,441-451.
1. Zhou, P.; Tian, F.; Zou, J.; Ren, Y.; Liu, X.; Shang, Z. Do halide motifs stabilize protein architecture? J. Phys. Chem. B 2010,114,15673-15686.
2. Lund. M.; Jungwirth, P.; Woodward, C. E. Ion specific protein assembly and hydrophobic surface forces. Phys. Rev. Lett.2008,100,258105.
3. Bostrom, M.; Williams, D.; Ninham, B. W. Specific ion effects:why DLVO theory fails for biology and colloid systems. Phys. Rev. Lett.2001,87,168103.
4. Kumar, S.; Nussinov, R. Close-range electrostatic interactions in proteins. ChemBioChem 2002,3,604-617.
5. Pervushin, K.; Billeter, M.; Siegal, G.; Wuthrich, K. Structural role of a buried salt bridge in the 434 repressor DNA-binding domain. J. Mol. Biol.1996,264, 1002-1012.
6. Lounnas, V.; Wade, R. C. Exceptionally stable salt bridges in cytochrome P450cam have functional roles. Biochemistry 1997,36,5402-5417.
7. Singh, U. C. Probing the salt bridge in the dihydrofolate reductase-methotrexate complex by using the coordinate-coupled free energy perturbation method. Proc. Natl Acad. Sci. USA 1988,85,4280-4284.
8. Sun, D. P.; Sauer, U.; Nicholson, H.; Matthews, B. W. Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. Biochemistry 1991,30,7142-7153.
9. Waldburger, C. D.; Schildbach, J. F.; Sauer, R. T. Are buried salt bridges important for protein stability and conformational specificity? Nat. Struct. Biol. 1995,2,122-128.
10. Netz, R. R. Water and ions at interfaces. Curr. Opin. Colloid Interface Sci.2004, 9,192-197.
11. Mahanty, J.; Ninham, B. W. Dispersion Forces; London:Academic Press, 1976.
12. Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S. H.; Chong, L.; Lee, M.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J., Case, D. A.; Cheatham, T. E. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc. Chem. Res.2000, 33,889-897.
13. Menikarachchi, L. C.; Gascon, J. A. QM/MM approaches in medicinal chemistry research. Curr. Top. Med. Chem.2010,10,46-54.
14. Krivov, G. G.; Shapovalov, M. V.; Dunbrack Jr, R. L. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 2009,77,778-795.
15. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
16. Bas, D. C.; Rogers, D. M.; Jensen, J. H. Very fast prediction and rationalization of pKa values for protein-ligand complexes. Proteins 2008,73,765-783.
17. Derjaguin, B. V. On the role of electrostriction terms in ionic electrostatic repulsion electrostatic component of the disjoining pressure. J. Colloid Interface Sci.1976,56,492-494.
18. Sizonenko, V. L. The role of image charge in ionic-electrostatic interactions of proteins and membranes. Biofizika 1995,40,1251-1255.
19. Ninham, B. W.; Yaminsky, V. Ion binding and ion specificity:the Hofmeister effect and Onsager and Lifshitz theories. Langmuir 1997,13,2097-2108.
20. Eriksson, A. E.; Baase, W. A.; Zhang, X. J.; Heinz, D. W.; Blaber, M.; Baldwin, E. P.; Matthews, B. W. Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. Science 1992,255, 178-183.
21. Rocchia, W.; Alexov, E.; Honig, B. Extending the applicability of the nonlinear. Poisson-Boltzmann equation:multiple dielectric constants and multivalent ions. J. Phys. Chem.2001,105,6507-6514.
22. Gilson, M. K.; Sharp, K. A.; Honig, B. H. Calculating the electrostatic potential of molecules in solution:method and error assessment. J. Comput. Chem.1987, 9,327-335.
23. Sitkoff, D.; Sharp, K. A.; Honig, B. Accurate calculation of hydration free energies using macroscopic solvent models. J. Phys. Chem.1994,98, 1978-1988.
24. Noyes, R. Thermodynamics of ion hydration as a measure of effective dielectric properties of water. J. Am. Chem. Soc.1962,84,513-522.
25. Rashin, A. A.; Honig, B. Reevaluation of the Born model of ion hydration. J. Phys. Chem.1985,89,5588-5593.
26. Bostrom, M.; Ninham, B. W. Contributions from dispersion and Born self-free energies to the solvation energies of salt solutions. J. Phys. Chem. B 2004,108, 12593-12595.
27. Stokes, R. H. The van der Waals radii of gaseous ions of the noble gas structure in relation to hydration energies.J. Am. Chem. Soc.1964,86,979-982.
28. Nagle. J. K. Atomic polarizability and electronegativity. J. Am. Chem. Soc.1990, 112,4141-4141.
29. Parsons, D. F.; Ninham, B. W. Importance of accurate dynamic polarizabilities for the ionic dispersion interactions of alkali halides. Langmuir 2010,26, 1816-1823.
30. Lide, D. R. CRC Handbook of Chemistry and Physics,84th Edition; Florida: CRC Press,2003.
31. Marcus, Y. Ion Properties; New York:Marcel Dekker Press,1997.
32. Bostrom, M.; Ninham. B. W. Dispersion self-free energies and interaction free energies of finite-sized ions in salt solutions. Langmuir 2004,20,7569-7574.
33. Bostrom, M.; Ninham. B. W. Energy of an ion crossing a low dielectric membrane:the role of dispersion self-free energy. Biophys. Chem.2005,114, 95-101.
34. Boroudjerdi, H.; Kim, Y. W.; Naji, A.; Netz, R. R.; Schlagberger, X.; Serr. A. Statics and dynamics of strongly charged soft matter. Phys. Rep.2005,416, 129-199.
35. Sanner, M. F.; Olson, A. J.; Spehner, J. C. Reduced surface:an efficient way to compute molecular surfaces. Biopolymers 1996, 38, 305-320.
36.Vreven, T.; Byun, K. S.; Komaromi, I.; Dapprich, S.; Montgomery, J. A.; Morokuma, K.; Frisch, M. J. Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J. Chem. Theory Comput. 2006, 2, 815-826.
37.Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T. Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 03; Gaussian, Inc.: Wallingford, CT, 2003.
38.Curtiss, L. A.; Raghavachari, K.; Trucks, G. W.; Pople, J. A. Gaussian-2 theory for molecular energies of first- and second-row compounds. J. Chem. Phys. 1991, 94, 7221-7230.
39.Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, Jr, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 1995,117, 5179-5197.
40.Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L, Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926-935.
41.Joung, I. S.; Cheatham Ⅲ, T. E. Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations. J. Phys. Chem. B 2008,112,9020-9041.
42. Kristyan, S.; Pulay, P. Can (semi) local density functional theory account for the London dispersion forces? Chem. Phys. Lett.,1994,229,175-180.
43. Johnson, E. R.; Wolkow, R. A.; DiLabio, G. A. Application of 25 density functionals to dispersion-bound homomolecular dimers. Chem. Phys. Lett.2004, 394,334-338.
44. Chesnut, D. B.; Moseley, R. W. The geometries of molecular complexes:an extended Huckel approach. Theor. Chim. Acta.1969,13,230-248.
45. Boys, S. F.; Bernardi, F. The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol. Phys.1970,19,553-566.
46. Janssen, D. B. Evolving haloalkane dehalogenases. Curr. Opin. Chem. Biol. 2004,8,150-159.
47. Verschueren, K. H. G.; Seljee, F.; Rozeboom, H. J.; Kalk, K. H.; Dijkstra, B. W. Crystallographic analysis of the catalytic mechanism of haloalkane dehalogenase. Nature 1993,363,693-698.
48. Schanstra, J. P.; Kingma, J.; Janssen, D. B. Specificity and kinetics of haloalkane dehalogenase. J. Biol. Chem.1996,271,14747-14753.
49. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
50. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol.1999,293,1241-1255.
51. Bostrom, M.; Williams, D. R. M.; Ninham, B. W. Specific ion effects:why the properties of lysozyme in salt solutions follow a Hofmeister series. Biophys. J. 2003,85,686-694.
52. Hendsch, Z. S.; Tidor, B. Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Sci.1994,3,211-226.
53. Zhou, P.; Ren, Y.; Tian, F.; Zou, J.; Shang, Z. Halogen-ionic bridges:do they exist in the biomolecular world? J. Chem. Theory Comput.2010,6,2225-2241.
54. Amico, D.; Gerday, S. C.; Feller, G. Structural similarities and evolutionary relationships in chloride-dependent a-amylases. Gene 2000,253,95-105.
55. Lesley, S. A.; Kuhn, P.; Godzik, A.; Deacon, A. M.; Mathews, I.; Kreusch, A.; Spraggon, G.; Klock, H. E.; McMullan, D.; Shin, T.; Vincent, J.; Robb, A.; Brinen, L. S.; Miller, M. D.; McPhillips, T. M.; Miller, M. A.; Scheibe, D.; Canaves, J. M.; Guda, C.; Jaroszewski, L.; Selby, T. L.; Elsliger, M.; Wooley, J.; Taylor, S. S.; Hodgson, K. O.; Wilson, I. A.; Schultz, P. G.; Stevens, R. C. Structural genomics of the Thermotoga maritime proteome implemented in a high-throughput structure determination pipeline. Proc. Natl Acad. Sci. USA 2002,99,11664-11669.
56. Pikkemaat, M. G.; Ridder, I. S.; Rozeboom, H. J.; Kalk, K. H.; Dijkstra, B. W.; Janssen, D. B. Crystallographic and kinetic evidence of a collision complex formed during halide import in haloalkane dehalogenase. Biochemistry 1999,38, 12052-12061.
57. Dagastine, R. R.; Prieve, D. C.; White, L.R. The dielectric function for water and its application to van der Waals forces. J. Colloid Interface Sci.2000,231, 351-358.
58. Ninham, B. W.; Parsegian, V. A. van der Waals forces. Special characteristics in lipid-water systems and a general method of calculation based on the Lifshitz theory. Biophys. J.1970,10,646-663.
59. Israelachvili, J. N. Intermolecular and Surface Forces; London:Academic Press, 1992.
60. Tavares, F. W.; Bratko, D.; Blanch, H. W.; Prausnitz. J. M. Ion-specific effects in the colloid-colloid or protein-protein potential of mean force:role of salt-macroion van der Waals interactions. J. Phys. Chem. B 2004,108, 9228-9235.
1. Zhou, P.; Tian, F.; Shang, Z.2D depiction of nonbonding interactions for protein complexes. J. Comput. Chem.2009,30,940-951.
2. Zhou, P.; Shang, Z.2D molecular graphics:a flattened world of chemistry and biology. Brief. Bioinform.2009,10,247-258.
3. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The protein data bank. Nucleic Acids Res.2000, 28,235-242.
4. Bader, G. D.; Hogue, C. W. BIND—a data specification for storing and describing biomolecular interactions, molecular complexes and pathways. Bioinformatics 2000,16,465-477.
5. Xenarios, I.; Rice, D. W.; Salwinski, L.; Baron, M. K.; Marcotte, E. M.; Eisenberg, D. DIP:the database of interacting proteins. Nucleic Acids Res.2000, 28,289-291.
6. Fischer, T. B.; Arunachalam, K. V.; Bailey, D.; Mangual, V.; Bakhru, S.; Russo, S.; Huang, D.; Paczkowski, M.; Lalchandani, V.; Ramachandra, C.; Ellison, B.; Galer, S.; Shapley, J.; Fuentes, E.; Tsai, J. The binding interface database (BID): a compilation of amino acid hot spots in protein interfaces. Bioinformatics 2003, 19,1453-1454.
7. Xenarios, I.; Eisenberg, D. Protein interaction databases. Curr. Opin. Biotech. 2001,12,334-339.
8. Dutta, S.; Berman, H. M. Large macromolecular complexes in the protein data bank:a status report. Structure 2005,13,381-388.
9. Clackson, T.; Wells, J. A. A hot spot of binding energy in a hormone-receptor interface. Science 1995,267,383-386.
10. Lawrence, M. C.; Colman, P. M. Shape complementarity at protein/protein interfaces. J. Mol. Biol.1993,234,946-950.
11. Aloy, P.; Russell, R. B. Ten thousand interactions for molecular biologist. Nat. Biotech.2004,22,1317-1321.
12. Chothia, C.; Janin, J. Principles of protein-protein recognition. Nature 1974, 256,705-708.
13. Horn, J. R.; Ramaswamy, S.; Murphy, K. P. Structure and energetics of protein-protein interactions:the role of conformational heterogeneity in OMTKY3 binding to serine proteases. J. Mol. Biol.2003,331,497-508.
14. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT:a program to generate schematic diagrams of protein-ligand interactions. Protein Eng.1995, 8,127-134.
15. Stierand, K.; MaaB, P. C.; Rarey, M. Molecular complexes at a glance: automated generation of two-dimensional complex diagrams. Bioinformatics 2006,22,1710-1716.
16. Clark, A. M.; Labute, P.2D depiction of protein-ligand complexes. J. Chem. Inf. Model.2007,47,1933-1944.
17. Luscombe, N. M.; Laskowski, R. A.; Thornton, J. M. NUCPLOT:a program to generate schematic diagrams of protein-nucleic acid interactions. Nucleic Acids Res.1997,25,4940-4945.
18. Finn, R. D.; Marshall. M.; Bateman, A. iPfam:visualization of protein-protein interactions in PDB at domain and amino acid resolutions. Bioinformatics 2005, 27,410-412.
19. Salerno, W. J.; Seaver, S. M.; Armstrong, B. R.; Radhakrishnan, I. MONSTER: inferring non-covalent interactions in macromolecular structures from atomic coordinate data. Nucleic Acids Res.2004,32, W566-W568.
20. Mancini, A. L.; Higa, R. H.; Oliveira, A.; Dominiquini, F.; Kuser, R. R.; Yamagishi, M. E. B.; Togawa, R. C.; Neshich, G. STING contacts:a web-based application for identification and analysis of amino acid contacts within protein structure and across protein interfaces. Bioinformatics 2004,20,2145-2147.
21. Sobolev, V.; Sorokine, A.; Prilusky, J.; Abola, E. E.; Edelman, M. Automated analysis of interatomic contacts in proteins. Bioinformatics 1999,15, 327-332.
22. Fischer, T. B.; Holmes, J. B.; Miller, I. R.; Parsons, J. R.; Tung, L.; Hu, J. C.; Tsai, J. Assessing methods for identifying pair-wise atomic contacts across binding interfaces. J. Struct. Biol.2006,153,103-112.
23. McConkey, B. J.; Sobolev, V.; Edelman, M. Quantification of protein surfaces, volumes and atom-atom contacts using a constrained Voronoi procedure. Bioinformatics 2002,18,1365-1373.
24. Cootes, A. P.; Curmi, P. M. G.; Cunningham, R.; Donnelly, C.; Torda, A. E. The dependence of amino acid pair correlations on structural environment. Proteins 1998,32,175-189.
25. Reva, B. A.; Finkelstein, A. V.; Sanner, M. F.; Olson, A. J. Residue-residue mean-force potentials for protein structure recognition. Protein Engin.1997,10, 865-876.
26. Williams, G.; Doherty, P. Inter-residue distances derived from fold contact propensities correlate with evolutionary substitution costs. BMC Bioinformatics 2004,5,153.
27. Kazmierkiewicz, R.; Liwo, A.; Scherag, H. A. Addition of side chains to a known backbone with defined side chain centroids. Biophys. Chem.2003,100, 261-280.
28. Zhou, H.; Zhou, Y. Stability scale and atomic solvation parameters extracted from 1023 mutation experiments. Proteins 2002,49,483-492.
29. Zhang, C.; Vasmatzis, G.; Cornette, J. L.; DeLisi C. Determination of atomic desolvation energies from the structures of crystallized proteins. J. Mol. Biol. 1997,267,707-726.
30. Lo Conte, L.; Chothia, C.; Janin, J. The atomic structure of protein-protein recognition sites. J. Mol. Biol.1999,285,2177-2198.
31. Word, J. M.; Lovell, S. C.; Richardson, J. S.; Richardson, D. C. Asparagine and glutamine:using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol.1999,285,1735-1747.
32. McDonald, I. K.; Thornton, J. M. Satisfying hydrogen bonding potential in proteins. J. Mol. Biol.1994,238,777-793.
33. Word, J. M.; Lovell, S. C.; LaBean, T. H.; Taylor, H. C.; Zalis, M. E.; Presley, B. K.; Richardson, J. S.; Richardson, D. C. Visualizing and quantifying molecular goodness-of-fit:small-probe contact dots with explicit hydrogen atoms. J. Mol. Biol. 1999,285,1711-1733.
34. Sanner, M. F.; Olson, A. J.; Spehner, J. C. Reduced surface:an efficient way to compute molecular surfaces. Biopolymers 1996,38,305-320.
35. Rocchia, W.; Alexov, E.; Honig B. Extending the applicability of the nonlinear Poisson-Boltzmann equation:multiple dielectric constants and multivalent ions. J. Phys. Chem. B 2001,105,6507-6514.
36. Vriend, G. WHATIF:a molecular modeling and drug design program. J. Mol. Graph.1990,8,52-56.
37. Canutescu, A. A.; Shelenkov, A. A.; Dunbrack Jr, R. L. A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci.2003,12, 2001-2014.
38. Brunger, A. T.; Kuriyan, J.; Karplus, M. Crystallographic R factor refinement by molecular dynamics. Science 1987,235,458-460.
39. Boobbyer, D. N. A.; Goodford, P. J.; McWhinnie, P. M.; Wade, R. C. New hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structure. J. Med. Chem.1989,32,1083-1094.
40. Goodford, P. J. A computational procedure for determining energetically favorable binding sites on biologically important molecules. J. Med. Chem. 1985,28,849-857.
41. Vedani, A.; Dunitz, J. D. Lone-pair directionality in hydrogen bond potential functions for molecular mechanics calculations. J. Am. Chem. Soc.1985,107, 7653-7658.
42. Brooks, B. R.; Bruccoleri, R.E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. CHARMM:a program for macromolecular energy, minmimization, and dynamics calculations. J. Comput. Chem.1983,4,187-217.
43. Huey, R.; Morris, G. M.; Olson, A. J.; Goodsell, D. S. A semiempirical free energy force field with charge-based desolvation. J. Comput. Chem.2007,28, 1145-1152.
44. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz Jr, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc.1995,117,5179-5197.
45. Hirschfelder, J.; Roseveare, W. Intermolecular forces and the properties of gases. J. Phys. Chem.1939,43,15-35.
46. de Vries, S. J.; Bonvin, A. M. J. Intramolecular surface contacts contain information about protein-protein interface regions. Bioinformatics 2006,22, 2094-2098.
47. Bondi, A. van der Waals volumes and radii.J. Phys. Chem.1964,68,441-451.
48. Chothia, C. Structural invariants in protein folding. Nature 1975,254,304-308.
49. Li, A. J.; Nussinov, R. A set of van der Waals and Coulombic radii of protein atoms for molecular and solvent-accessible surface calculation, packing evaluation, and docking. Proteins 1998,32,111-127.
50. Eisenberg, D.; McLachlan, A. D. Solvation energy in protein folding and binding. Nature 1986,319,199-203.
51. Juffer, A. H.; Eisenhaber, F.; Hubbard, S. J.; Walther, D.; Argos, P. Comparison of atomic solvation parametric sets:applicability and limitations in protein folding and binding. Protein Sci.1995,4,2499-2509.
52. Kim, A. Amino acid side chain contributions to free energy of transfer of tripeptides from water to octanol [dissertation]. San Francisco, California: University of California,1990.
53. Schiffer, C. A.; Caldwell, J. W.; Kollman, P. A.; Stroud, R. M. Protein structure prediction with a combined solvation free energy-molecular mechanics force field. Mol. Simul.1993,10,121-149.
54. Kumar, S.; Nussinov, R. Salt bridge stability in monomeric proteins. J. Mol. Biol.1999,293,1241-1255.
55. Kumar, S.; Nussinov, R. Close range electrostatic interactions in proteins. ChemBioChem 2002,3,604-617.
56. Sarakatsannis, J. N.; Duan, Y. Statistical characterization of salt bridges in proteins. Proteins 2005,60,732-739.
57. Hendsch, Z. S.; Tidor, B. Do salt bridges stabilize proteins? A continuum electrostatic analysis. Protein Sci.1994,3,211-226.
58. Hendsch, Z. S.; Sindelar, C. V.; Tidor, B. Parameter dependence in continuum electrostatic calculations:a study using protein salt bridges J. Phys. Chem. B 1998,102,4404-4410.
59. Sitkoff, D.; Sharp, K. A.; Honig, B. Accurate calculation of hydration free energies using macroscopic solvent models. J. Phys. Chem.1994,98, 1978-1988.
60. Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta Jr, S.; Weiner, P. A new force field for molecular mechanical simulation of nucleic acids and proteins. J. Am. Chem. Soc.1984,106,765-784.
61. MacKerell Jr, A. D.; Bashford, D.; Bellott, M.; Dunbrack Jr, R. L.; Evanseck, J. D.; Field, M. J.; Fischer, S.; Gao, J.; Guo, H.; Ha, S.; Joseph-McCarthy, D.; Kuchnir, L.; Kuczera, K.; Lau, F. T. K.; Mattos, C.; Michnick, S.; Ngo, T.; Nguyen, D. T.; Prodhom, B.; Reiher Ⅲ, W. E.; Roux, B.; Schlenkrich, M.; Smith, J. C.; Stote, R.; Straub, J.; Watanabe, M.; Wiorkiewicz-Kuczera, J.; Yin, D.; Karplus, M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 1998,102,3586-3616.
62. Kumar, S.; Nussinov, R. Relationship between ion pair geometries and electrostatic strengths in proteins. Biophys. J.2002,83,1595-1612.
63. D'Aquino, J. A.; Gomez, J.; Hilser, V. J.; Lee, K. H.; Amzel, L. M.; Fieire, E. The magnitude of the backbone conformational entropy change in protein folding. Proteins 1996,25,143-156.
64. Brady, G. P.; Sharp, K. A. Entropy in protein folding and in protein-protein interactions. Curr. Opin. Struct. Biol.1997,7,215-221.
65. Doig, A. J.; Sternberg, M. J. E. Side-chain conformational entropy in protein folding. Protein Sci.1995,4,2247-2251.
66. Creamer, T. P. Side-chain conformational entropy in protein unfolded states. Proteins 2000,40,443-450.
67. Koehl, P.; Delarue, M. Application of a self consistent mean field theory to predict protein side-chain conformations and estimate their conformational entropy. J. Mol. Biol.1994,239,249-275.
68. Karplus, M.; Ichiye, T.; Pettitt, B. M. Configurational entropy of native proteins. Biophys. J.1987,52,1083-1085.
69. Chellgren, B. W.; Creamer, T. P. Side-chain entropy effects on protein secondary structure formation. Proteins 2006,62,411-420.
70. Lovell, S. C.; Word, J. M.; Richardson, J. S.; Richardson, D. C. The penultimate rotamer library. Proteins 2000,40,389-408.
71. Dunbrack Jr, R. L. Rotamer libraries in the 21st century. Curr. Opin. Struct. Biol. 2002,12,431-440.
72. Zhang, J.; Liu, J. S. On side-chain conformational entropy of proteins. PLoS Comput. Biol.2006,2,1586-1591.
73. Chowdry, A. B.; Reynolds, K. A.; Hanes, M. S.; Voorhies, M.; Pokala, N.; Handel, T. M. An object-oriented library for computational protein design. J. Comput. Chem.2007,28,2378-2388.
74. Tsai, J.; Taylor, R.; Chothia, C.; Gerstein, M. The packing density in proteins: standard radii and volumes. J. Mol. Biol.1999,290,253-266.
75. McGaughey, G. B.; Gagne, M.; Rappe, A. K. p-stacking interactions, alive and well in protein. J. Boil. Chem.1998,273,15458-15463.
76. Cho, K.; Lee, K.; Lee, K. H.; Kim, D.; Lee, D. Specificity of molecular interactions in transient protein-protein interaction interfaces. Proteins 2006,65, 593-606.
77. Sun, S.; Bernstein, E. R. Aromatic van der Waals clusters:structure and nonrigidity. J. Phys. Chem.1996,100,13348-13366.