肌质网钙泵作用机理的相关问题研究
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摘要
骨骼肌内质网中的钙离子跨膜传输是一个通过钙泵和钙离子通道的形式传输钙离子的过程,它在控制肌肉收缩和生热方面都有非常重要的作用,其活性的大小是各种细胞能量代谢及功能有无损伤的重要指标。人体内钙泵的失调可以导致多种疾病的发生,但现在对于钙泵和钙通道的作用机制尚无明确的认识。此外,钙离子的跨膜传输过程还有待于进一步的考察。本论文围绕着生物体中钙离子跨膜传输过程中所涉及的与肌质网钙泵和钙通道有关的功能区域分子构象的变化、能量传递、钙离子与各活性位点的耦合作用以及离子选择性等有关问题,用理论化学方法深入研究了钙泵和钙通道的功能原理和本质。同时,结合构效分析及分子间各类强弱相互作用的研究,探讨了氨基酸残基、溶剂分子等环境因素和结构因素等对钙离子传输机制的影响和调控作用,并取得了一些有意义的研究成果,为认识离子泵和离子通道提供了重要的理论信息。主要的研究成果与创新简述如下:
酸性氨基酸与钙离子的耦合特征及其生物意义Ca~(2+)-ATP酶中的酸性氨基酸在Ca~(2+)跨膜传输过程中有重要的作用,它们既可以作为耦合配体直接参与反应,又可作为探测Ca~(2+)结合与否的“探测器”。因此,在本论文中,我们首先系统考察了具有酸性边链的谷氨酸分子和Ca~(2+)的相互作用及其生物意义。密度泛函理论的研究结果表明,在气相中,存在16种稳定的谷氨酸-Ca~(2+)异构体,分别对应着谷氨酸配体和Ca~(2+)的三齿、双齿和单齿耦合的构型特征。其中最稳定的构象对应着Ca~(2+)与三个氧原子(分别为边链的两个羧基氧和一个主链羰基氧)相互作用的模式,并且在结合Ca~(2+)的同时伴随着一个质子转移的现象。次稳定的构象也对应着一个三齿耦合的形式(Ca~(2+)与两个羰基氧和一个氨基氮相互作用),它的能量仅比最稳定的复合物高2.1 kcal/mol。所有复合物的构型和能量特征都从耦合形式、相对能、静电作用、形变能、电荷布局分析、轨道键合特征和分子内氢键等方面进行了研究。结果表明,谷氨酸的三个活性官能团与Ca~(2+)的结合能力如下:羰基氧＞氨基氮＞羟基氧。另外,谷氨酸总是以尽可能多的活性基团与Ca~(2+)进行耦合。由于构型和能量上的相似性,不同复合物之间的相互转化也极易发生。实际生命过程中的肌质网Ca~(2+)跨膜传导细节可以用我们的计算结果解释如下:当Ca~(2+)-ATPase处于E1构型,即Ca~(2+)结合在高亲和位点时,谷氨酸会与Ca~(2+)以较大的强度进行耦合,此时对应的复合物形式为三齿或双齿耦合;当Ca~(2+)-ATP酶转化到具有低亲和位点的E2构型时,谷氨酸-Ca~(2+)会以不稳定的形式(如单齿耦合模式)存在,因为此种耦合形式有利于Ca~(2+)从结合位释放到内腔中。此外,频率分析表明,在复合物中,C=O伸缩振动模式具有最大强度的红外吸收峰,并且在结合了Ca~(2+)之后,这些峰都会红移。
谷氨酸-钙离子复合物的逐步水合效应及其生物意义在实际的生命体中,反应都是在溶液或蛋白环境下进行的。而在溶剂分子的作用下,金属离子-配体的作用模式会与气态中有所区别。为了更好地接近于真实的生命过程,我们又采用密度泛函理论(DFT)研究了逐步水合对谷氨酸-Ca~(2+)体系的影响。研究内容包括水合反应的热力学参数,逐步水合能及精确的构型信息等。同时,为了进一步考察水合作用的影响,本文也对相关的电荷转移、键合分析以及红外光谱特征进行了研究。计算结果表明,在静电作用、电荷转移、电子轨道效应和离子-配体、配体-配体排斥力的共同影响下,水分子的增加削弱了Ca-O键的强度,并导致了(C-)O-Ca-O(-C)键角的减小。而当水分子同时结合在Ca~(2+)的第一耦合层和第二耦合层时,外围的水合使得内层水分子靠近Ca~(2+),而内层的羧基氧逐渐远离Ca~(2+)。此外,由于氢键作用的增加,逐步水合过程可以使谷氨酸-Ca~(2+)体系变得更稳定。所有的逐步水合反应均为焓驱动过程,但是当耦合的水分子位于第一层时,这种逐步水合过程并不能无限制地进行下去,而是有一个最大的水合数。本文的研究数据表明此数值为6或7。在蛋白质数据库(PDB)中,Ca~(2+)的平均耦合数也为6,而在可溶性的生物体钙蛋白中,最常见的耦合数为7,与我们的计算结果相一致。同时,溶剂化模型计算(SCRF)和高水平的MP2计算也证实了计算结果的准确性。在计算过程中,还发现了一个非常重要的配体交换的现象,即:无论水分子耦合在Ca~(2+)的第一层还是第二层,随着耦合数的增加,它们都会逐步削弱谷氨酸和Ca~(2+)的作用强度,直至其中的一个耦合水分子代替谷氨酸配体的位置,使谷氨酸由内层耦合模式转变为外层耦合模式。在真实的肌质网钙通道中,Ca~(2+)处于蛋白质空穴中,为氨基酸残基所包围:而当其经由Ca~(2+)释放通道进入内腔时,内腔中的水分子会部分或全部代替原来的氨基酸残基。此过程与我们的模拟计算过程是及其类似的,因此我们的研究完全可以提供相关的理论数据来加深人们对于Ca~(2+)通道作用的理解。另外,我们还对所采用的计算模型与实际生物体中肌质网钙通道的相似性和不同点进行了比较研究。
离子选择性的本质及其影响因素在Mg~(2+)浓度比Ca~(2+)浓度高数千倍的情况下,肌质网Ca~(2+)-ATPase仍可以特异性地选择Ca~(2+)进行跨膜传导。离子选择性是Ca~(2+)-ATPase的一个重要特征。我们所进行的密度泛函的计算结果表明,无论是由脂肪族还是芳香族氨基酸组成的蛋白空穴都更容易结合Mg~(2+)而非Ca~(2+),这主要是由Mg~(2+)和配体之间更强的静电相互作用引起的。进一步的研究表明,氨基酸对于水合阳离子的亲合力受金属离子的特性、氨基酸配体的电负性和结合模式等因素的影响。相对于Ca~(2+)来说,Mg~(2+)有更小的半径和更大的电荷密度。因此,如果结合到同一个配体上,Mg~(2+)会表现出比Ca~(2+)更强的静电相互作用。另一方面,当配体的电负性增加时,它们都对Mg~(2+)表现出了更大的亲合力。同时,配体对于Ca~(2+)和Mg~(2+)的区分能力也相应提高。我们的研究结果表明,配体对于Ca~(2+)和Mg~(2+)的区分能力如下:“吲哚-乙酸”协同耦合＞“吲哚-甲酰胺”协同耦合＞“吲哚-吲哚”协同耦合＞“吲哚”耦合。此外,配体的不同结合模式也会影响离子选择性。在“吲哚”耦合和“吲哚-吲哚”协同耦合模式中,吲哚分子结合在第二层时所对应的反应具有最大的离子选择性;而对于“吲哚-乙酸”和“吲哚-甲酰胺”协同耦合模式,吲哚分子结合在第二层,同时单齿脂肪族配体键合第一层时所对应的反应具有最大的离子选择性。更重要的是,我们的计算可用来解释肌质网中Ca~(2+)的选择性机理:当水合Ca~(2+)和水合Mg~(2+)靠近Ca~(2+)-ATP酶时,酶-水界面上的蛋白空穴会优先结合Mg~(2+),导致Mg~(2+)的浓度在局部区域内降低,而这时游离的Ca~(2+)就相对较多。即使有键合的Ca~(2+),其与配体之间较弱的结合力也会使得它们很容易被释放,因此Ca~(2+)可以相对容易地进入Ca~(2+)-ATP酶中的离子传输通道。对于极少数随Ca~(2+)进入通道的Mg~(2+),配体对于Mg~(2+)的强亲合阻止了这个离子的自由传导,而结合较弱的Ca~(2+)则可以以较高的速率通过Ca~(2+)-ATP酶的跨膜区域。此现象与以前报导的“sticky-pore”假说相一致。另外一个影响Ca~(2+)和Mg~(2+)选择性的因素是结合位点空穴的大小和结合位点处的配体在结合阳离子时所能提供的配位数。研究发现,在高亲和位点Ⅰ和Ⅱ处,位点空穴大小和结合位点处的七配位特征更有利于Ca~(2+)的耦合。对于价态不同的Na~+、K~+和Ca~(2+),有如下的几个离子选择性机理(以Na~+和Ca~(2+)为例):第一,一个Ca~(2+)和两个Na~+拥有相同的电荷中和能力,却占有更小的空间,同时由于通道狭小的空间,更倾向于结合Ca~(2+);第二,在传导过程中,若有Na~+、K~+占据配位点,由于Ca~(2+)与配体有更强的相互作用,它可以很容易地取代一价离子,从而占据配位点。第三,配位点处的配体耦合数不适于Na~+的结合。
非键结合模式在钙离子传导过程中的作用非键作用在生命体中广泛存在,而其中的阳离子-π耦合模式在Ca~(2+)-ATP酶、K~+通道和季铵盐通道抑制剂等方面都有重要的作用。因此,我们用二阶微扰的方法计算了与肌质网钙泵和钙通道相关的Ca~(2+)-π相互作用和脂肪族氨基酸参与的Ca~(2+)-π相互作用。计算结果表明,芳香性分子所具有的离域π键特征使得它们成为结合Ca~(2+)的良好配体。而脂肪族氨基酸边链参与反应之后,可以极大地提高Ca~(2+)-配体之间的作用强度。具体来说,对于Ca~(2+)-π复合物,我们研究了Ca~(2+)分别与一到三个苯分子的耦合特征。当Ca~(2+)与两个苯环相互作用时,所对应的最低能量构型是一个交错平行的三明治结构;而当Ca~(2+)与三个苯环作用时,所对应的最低能量构型是一个笼状的结构。很明显,这些结构都具有最小的配体排斥力,并且能够有效地稳定复合物体系。同样的现象也发生在甲酰胺和乙酸耦合的Ca~(2+)-π复合物中。值得注意的是,当甲酰胺直接与苯分子结合时,它对苯环的芳香性特征几乎没有什么影响,而乙酸与苯环的结合则会削弱苯环的芳香性特征。这一点可以从NBO分析和键合轨道分析中反映出来。本章计算结果所体现的最重要的一点是:与脂肪族边链相比,芳香族边链对Ca~(2+)的结合能力更小。而在与肌质网相关的Ca~(2+)传导过程中,达到结合-释放平衡是非常重要的。芳香性分子对Ca~(2+)更弱的亲合使得Ca~(2+)可以更容易从结合的配体中释放出来,从而达到结合-释放的微妙平衡。因此,我们认为芳香性氨基酸在Ca~(2+)传导过程中应该起到了重要的作用。除此之外,Ca~(2+)的结合可以减小蛋白配体的HUMO-LUMO能差,从而导致荧光现象的发生。这一点可以为实验学家们研究Ca~(2+)的结合位点和传导过程提供理论信息和帮助。
In skeletal muscle,the calcium ions transport against a concentration gradient from the cytoplasm into the sarcoplasmic reticulum by Ca~(2+)pump and Ca~(2+)-channel, which can control the muscles' contraction and the heat production.In addition,the activity of the Ca~(2+)conductivity can signal the metabolism of various cells efficiently. Thus the maladjustment of the Ca~(2+)pump would result in many diseases and the corresponding work must be done as soon as possible.By now,the mechanism of the Ca~(2+)pump and Ca~(2+)-channel remains ambiguous.Thus,in the present doctoral dissertation,the relative studies on the geometrical changes,energetic transmission, and the coupling mechanisms between Ca~(2+)ions and the main active sites of Ca~(2+) pump have been systematically and extensively investigated employing the theoretical chemistry menthods.Additionally,the specificity and selectivity of Ca~(2+)have also be studied to explore the functions and interactive essence of the Ca~(2+)pump and Ca~(2+)-channel.Besides,the environmental factors,such as the peripheral amino acid and solvent effects,have also been investigated.Upon these studies,the corresponding mechanical models and thermodynamics parameters to describe the Ca~(2+)transport have been established elaborately.As a result,some significant progresses have been made,which can be described as follows.
(?)Coupling Character Between the Acidic Amino Acid Residues and Ca~(2+)and the Corresponding Biological Implicaitons Among the amino acid residues in the sarcoplasmic reticulum(SR)Ca~(2+)-ATPase,glutamic acid has played the important roles on the process of the Ca~(2+)transmembrane conductivity.On one hand,it paricipates the Ca~(2+)coupling in the high-affinity sites;and on the other hand,it is likely to be able to "sense" if siteⅡis occupied by Ca~(2+).So,glutamic acid could be part of the Ca~(2+)channel.In the present doctoral dissertation,we have investigated the biological relevant glutamic acid-Ca~(2+)bonding with density functional theory calculations.Sixteen chelating modes,which are divided into three different chelating types,that is,tridentate,bidentate,and monodentate forms,have been found.Among these isomers,the lowest energy structure is a zwitterionic form,
corresponding to Ca~(2+)interacting with three carbonyl oxygen atoms.Another tridentate form,with a bonding property of the calcium cation interacting with two carbonyl oxygen atoms and one amino nitrogen,is only 2.1 kcal/mol higher in energy. The geometrical character and relative stability of all isomers have been analyzed from the aspects of coupling forms,relative energies,electrostatic interactions, deformation energies,charge distributions,bonding characters,and intramolecular H-bonds.Results indicate that,among three active groups in glutamic acid,the binding ability order is the carbonyl O＞the amino N＞the hydroxyl O,and the main binding character is that Ca~(2+)couples with glutamic acid as in the multidentate form as possible.Became of the similarity in geometry and energy,the geometric transformation mechanisms among different structures have been explored.In actual biological processes of Ca~(2+)transport,the residues around Ca~(2+)have undergone conformational changes,which can be partly explained by our research:when Ca~(2+) binds to the high-affinity binding sites of El conformation of SR Ca~(2+)-ATPase,the glutamic acid chelates with Ca~(2+)in a stable form like the tri- or bidentate forms;but when Ca~(2+)-ATPase changes to the low-affinity conformation,the glutamic acid-Ca~(2+) chelate is in an unstable form,such as the monodentate geometry,thus release the calcium cation easily.Moreover,harmonic vibrational frequencies and their corresponding infrared frequencies have been determined for chelates in the gas-phase employing the B3LYP/6-31+G(d,p)level of theory.The frequency analyses indicate that the biggest vibratioanl intensity peak corresponds to the C=O stretching mode and it is red-shifted after it binds with Ca~(2+).
(?)Effects of the Stepwise Hydration on the Glutamic Acid-Ca~(2+)
Complexes and the Corresponding Biological Implicaitons In vivo,the complexes exist in the bulk solvent.Considering the effect of water,some different phenomena may take place for the glutamic acid-Ca~(2+)complexes.To approach the real biological processes,the stepwise hydration effects on the glutamic acid-Ca~(2+) complexes have been investigated systematically by employing the B3LYP density functional theory method with the 6-31+G(d,p)and 6-311++G(2d,p)basis sets.The thermodynamics parameters for the hydration reactions,the stepwise hydration energies,and accurate geometries have been explored.To elucidate the Ca~(2+)-ligand interaction,the charge transfer,bonding analysis,and IR spectroscopic characteristics have also been investigated.The calculated resultes have revealed that the stepwise hydration has caused a series of geometrical changes on the glutamic acid-Ca~(2+) complexes.Influenced by the ion-ligand electrostatic interaction,charge transfer from ligand to ion,electronic orbital effects,ion-ligand and ligand-ligand repulsions,the increase of the water molecules in the first shell has weakened the Ca~(2+)-O bond strength,which also results in the decrease of the(C-)O-Ca~(2+)-O(-C)bond angles. Notably,in the first-and-second-shell coordination mode,the peripheral hydration has caused the calcium cation to move closer to the first-shell water molecules,but increased the distance between Ca~(2+)and the carboxylic oxygen atoms.Additionally, because of the increase of the H-bonds,the stepwise hydration has stabilized the glutamic acid-Ca~(2+)complexes.The correlating data have shown that all of the stepwise hydration reactions are enthalpy-driven because of the relatively small value of△S,but the number of coordinated water molecules in the first shell of Ca~(2+)is not limitless.In our study,the optimal coordination number(CN)of Ca~(2+)in the first shell is 6 or 7;the former value agrees well with the datum reported in the Protein Data Bank(PDB),and the latter is the reflection of the most frequent Ca~(2+)-binding motif, EF-hand,in soluble proteins.Furthermore,the self-consistent reaction field(SCRF) and higher-level MP2 calculations have confirmed our conclusions.Additionally and very importantly,the stepwise hydration in either the first or second coordination shell can weaken the glutamic acid-Ca~(2+)interaction gradually till the glutamic acid ligand is replaced by the added water molecules,resulting in the conversion of coordination mode of the glutamic acid to Ca~(2+)from the inner-sphere one to a peripheral interaction mode,just like the ligand exchange process in the Ca~(2+)release channel existing in the real biological system.Finally,the similarities and discrepancies between our model and the Ca~(2+)-channel in vivo have been compared.
(?)Essence of the Ion Selectivity and the Influence Factors As reported previously,the SR Ca~(2+)-ATPase selectively transports Ca~(2+)in the presence of 10~3-10~5=fold higher concentrations of Mg~(2+).However,the selective mechanisms of the Ca~(2+)-ATPase to the calcium ions against the magnesium ions remain ambiguous, and much fewer studies on the basis of the physicochemical characteristics have been reported.Thus,we investigated the nature of the different amino acid residues interacting with the biologically active Ca~(2+)and Mg~(2+)and the selective transportation of Ca~(2+)over Mg~(2+)at the enzyme-water interface and in the entrance channel of the SR Ca~(2+)-ATPase.The calculated results demonstrate that the electronegative protein cavities,composed of either aliphatic or aromatic amino acids,at the enzyme-water interface and in the entrance channel prefer to bind Mg~(2+)rather than Ca~(2+)due to the stronger electrostatic interactions between Mg~(2+)and ligands.Further investigations show that the affinities of amino acids to the hydrated cations depend on the nature of the metal cations and the electronegativity and binding mode(the first- vs second=shell binding;mono-vs bidentate binding)of the amino acid ligands.In detail, relative to Ca~(2+),Mg~(2+)has a stronger electrostatic interaction to the same ligands because of its smaller radius and bigger charge density.On the other hand,when the electronegativity of the ligand increases,the ligand exhibits a bigger affinity to Mg~(2+). Simultaneously,discrimination of the ligands between Ca~(2+)and Mg~(2+)is also enhanced.For the studied cases,the order of the ligand discrimination between Ca~(2+) and Mg~(2+)are as follows:Trp-Glu＞Trp-Gln＞Trp-Trp＞Trp.In addition,the ligand binding modes have essential effects on ligand discrimination.In the Trp and Trp-Trp cases reactions with the biggest ion-selectivity are those which exhibit the second-shell indole binding,while for the Trp-Gln and Trp-Glu cases reactions with the biggest ion selectivity are those whose products have the second-shell indole and the first-shell monodentate aliphatic amino acids.More importantly,the calculations supplied feasible mechanisms to explain the size selectivity of Ca~(2+)over Mg~(2+). Concretely to say,when these two kinds of hydrated cations move to the vicinity of the SR Ca~(2+)-ATPase,the protein pockets at the enzyme-water interface bind Mg~(2+) more tightly than Ca~(2+),resulting in the concentration decrease of Mg~(2+)in the local region.Then Ca~(2+)transports into the entrance channel of the Ca~(2+)=ATPase favorably. As for the few Mg~(2+)ions,which may go into the entrance channel accompanying the Ca~(2+)current,the big affinity of the ligands to Mg~(2+)hampered the transportation of this cation freely,so the incompactly bound Ca~(2+)can transport through the transmembrane region of the Ca~(2+)-ATPase at a relatively high rate.This phenomenon is consistent with the "sticky-pore" hypothesis reported previously.Other very important factors to distinguish Ca~(2+)and Mg~(2+)are the size of the cavities formed by the binding sites and the preferred coordination number of these two cations. Additionally,the phenomenon of Ca~(2+)selectivity against much higher background concentrations of monovalent Na~+ and K~+ can be explainded as follows(take Na~+ for example):Firstly,Ca~(2+)ions have the same charge-neutralizing effect as two Na~+ ions while occupying less of the limited volume of the filter.Secondly,because the divalent calcium ions are more strongly attracted by the channel they can displace the sodium ions to occupy this region.Once there,Ca~(2+)can only be moved by the repulsion from another divalent ion and not by the lower repulsion from Na~+.Thirdly, the preferred coordination number of Na~+(6)and the average Na~+-O bond length (2.40(?))are unmatched to the Ca~(2+)channel.
(?)Effects of the Ca~(2+)-πNonvalent Interactions on the Ca~(2+)Transfer Nonvalent interactions exist in the biological processes extensively.Among them, cation-πinteraction has played the important roles in the Ca~(2+)-ATPase,K~+ channels, and quaternary ammonium inhibitors.Thus,we have studied the biologically relevant Ca~(2+)-πinteractions and aliphatic amino acid coupled Ca~(2+)-πinteractions by the Moller-Plesset calculations.The calculated results indicated that the delocalizedπcharacteristics make the aromatic molecules the active ligands to bind Ca~(2+). Furthermore,the participations of the side chains of the aliphatic amino acids enhanced the Ca~(2+)-ligands interactions greatly.For the Ca~(2+)-πcomplexes,we have investigated how Ca~(2+)bind to one up to three benzene molecules.When Ca~(2+)interacts with two benzene rings,the lowest energy structure is a staggered-parallel sandwich (SPS)form;while when Ca~(2+)interacts with three benznene molecules,the lowest energy structure corresponds to a caged(C)form.Inevitably,these cases have the smallest ligands repulsions,which can stabilize the systems effectively.The same phenomena occur in the formamide- and acetate-coupled Ca~(2+)-πcomplexes.Notably, when formamide binds the benzene molecule directly,it has few effect on the aromatic characteristics of benzene.In contrast,the binding of acetate to the benzene ring will weaken the aromatic characteristics of benzene,which can be verified by the NBO and orbital analyses.Most importantly,our calculations have revealed that the side chains of the aliphatic amino acids bind Ca~(2+)more strongly than those of the aromatic amino acids.Considerably,the weaker affinity of the aromatic iigands to Ca~(2+)has resulted in the easier desorption of this cation from the ligands.Thus the aromatic amino acids can play the important roles in the binding-release balance of Ca~(2+)in the Ca~(2+)-ATPase.In addition,the Ca~(2+)binding can reduce the HUMO-LUMO gaps of the protein ligands,resulting in the occurance of the fluorescence,which may be useful for the experimentalists to detect the Ca~(2+)binding sites and conductivity processes.
酸性氨基酸与钙离子的耦合特征及其生物意义Ca~(2+)-ATP酶中的酸性氨基酸在Ca~(2+)跨膜传输过程中有重要的作用,它们既可以作为耦合配体直接参与反应,又可作为探测Ca~(2+)结合与否的“探测器”。因此,在本论文中,我们首先系统考察了具有酸性边链的谷氨酸分子和Ca~(2+)的相互作用及其生物意义。密度泛函理论的研究结果表明,在气相中,存在16种稳定的谷氨酸-Ca~(2+)异构体,分别对应着谷氨酸配体和Ca~(2+)的三齿、双齿和单齿耦合的构型特征。其中最稳定的构象对应着Ca~(2+)与三个氧原子(分别为边链的两个羧基氧和一个主链羰基氧)相互作用的模式,并且在结合Ca~(2+)的同时伴随着一个质子转移的现象。次稳定的构象也对应着一个三齿耦合的形式(Ca~(2+)与两个羰基氧和一个氨基氮相互作用),它的能量仅比最稳定的复合物高2.1 kcal/mol。所有复合物的构型和能量特征都从耦合形式、相对能、静电作用、形变能、电荷布局分析、轨道键合特征和分子内氢键等方面进行了研究。结果表明,谷氨酸的三个活性官能团与Ca~(2+)的结合能力如下:羰基氧＞氨基氮＞羟基氧。另外,谷氨酸总是以尽可能多的活性基团与Ca~(2+)进行耦合。由于构型和能量上的相似性,不同复合物之间的相互转化也极易发生。实际生命过程中的肌质网Ca~(2+)跨膜传导细节可以用我们的计算结果解释如下:当Ca~(2+)-ATPase处于E1构型,即Ca~(2+)结合在高亲和位点时,谷氨酸会与Ca~(2+)以较大的强度进行耦合,此时对应的复合物形式为三齿或双齿耦合;当Ca~(2+)-ATP酶转化到具有低亲和位点的E2构型时,谷氨酸-Ca~(2+)会以不稳定的形式(如单齿耦合模式)存在,因为此种耦合形式有利于Ca~(2+)从结合位释放到内腔中。此外,频率分析表明,在复合物中,C=O伸缩振动模式具有最大强度的红外吸收峰,并且在结合了Ca~(2+)之后,这些峰都会红移。
谷氨酸-钙离子复合物的逐步水合效应及其生物意义在实际的生命体中,反应都是在溶液或蛋白环境下进行的。而在溶剂分子的作用下,金属离子-配体的作用模式会与气态中有所区别。为了更好地接近于真实的生命过程,我们又采用密度泛函理论(DFT)研究了逐步水合对谷氨酸-Ca~(2+)体系的影响。研究内容包括水合反应的热力学参数,逐步水合能及精确的构型信息等。同时,为了进一步考察水合作用的影响,本文也对相关的电荷转移、键合分析以及红外光谱特征进行了研究。计算结果表明,在静电作用、电荷转移、电子轨道效应和离子-配体、配体-配体排斥力的共同影响下,水分子的增加削弱了Ca-O键的强度,并导致了(C-)O-Ca-O(-C)键角的减小。而当水分子同时结合在Ca~(2+)的第一耦合层和第二耦合层时,外围的水合使得内层水分子靠近Ca~(2+),而内层的羧基氧逐渐远离Ca~(2+)。此外,由于氢键作用的增加,逐步水合过程可以使谷氨酸-Ca~(2+)体系变得更稳定。所有的逐步水合反应均为焓驱动过程,但是当耦合的水分子位于第一层时,这种逐步水合过程并不能无限制地进行下去,而是有一个最大的水合数。本文的研究数据表明此数值为6或7。在蛋白质数据库(PDB)中,Ca~(2+)的平均耦合数也为6,而在可溶性的生物体钙蛋白中,最常见的耦合数为7,与我们的计算结果相一致。同时,溶剂化模型计算(SCRF)和高水平的MP2计算也证实了计算结果的准确性。在计算过程中,还发现了一个非常重要的配体交换的现象,即:无论水分子耦合在Ca~(2+)的第一层还是第二层,随着耦合数的增加,它们都会逐步削弱谷氨酸和Ca~(2+)的作用强度,直至其中的一个耦合水分子代替谷氨酸配体的位置,使谷氨酸由内层耦合模式转变为外层耦合模式。在真实的肌质网钙通道中,Ca~(2+)处于蛋白质空穴中,为氨基酸残基所包围:而当其经由Ca~(2+)释放通道进入内腔时,内腔中的水分子会部分或全部代替原来的氨基酸残基。此过程与我们的模拟计算过程是及其类似的,因此我们的研究完全可以提供相关的理论数据来加深人们对于Ca~(2+)通道作用的理解。另外,我们还对所采用的计算模型与实际生物体中肌质网钙通道的相似性和不同点进行了比较研究。
离子选择性的本质及其影响因素在Mg~(2+)浓度比Ca~(2+)浓度高数千倍的情况下,肌质网Ca~(2+)-ATPase仍可以特异性地选择Ca~(2+)进行跨膜传导。离子选择性是Ca~(2+)-ATPase的一个重要特征。我们所进行的密度泛函的计算结果表明,无论是由脂肪族还是芳香族氨基酸组成的蛋白空穴都更容易结合Mg~(2+)而非Ca~(2+),这主要是由Mg~(2+)和配体之间更强的静电相互作用引起的。进一步的研究表明,氨基酸对于水合阳离子的亲合力受金属离子的特性、氨基酸配体的电负性和结合模式等因素的影响。相对于Ca~(2+)来说,Mg~(2+)有更小的半径和更大的电荷密度。因此,如果结合到同一个配体上,Mg~(2+)会表现出比Ca~(2+)更强的静电相互作用。另一方面,当配体的电负性增加时,它们都对Mg~(2+)表现出了更大的亲合力。同时,配体对于Ca~(2+)和Mg~(2+)的区分能力也相应提高。我们的研究结果表明,配体对于Ca~(2+)和Mg~(2+)的区分能力如下:“吲哚-乙酸”协同耦合＞“吲哚-甲酰胺”协同耦合＞“吲哚-吲哚”协同耦合＞“吲哚”耦合。此外,配体的不同结合模式也会影响离子选择性。在“吲哚”耦合和“吲哚-吲哚”协同耦合模式中,吲哚分子结合在第二层时所对应的反应具有最大的离子选择性;而对于“吲哚-乙酸”和“吲哚-甲酰胺”协同耦合模式,吲哚分子结合在第二层,同时单齿脂肪族配体键合第一层时所对应的反应具有最大的离子选择性。更重要的是,我们的计算可用来解释肌质网中Ca~(2+)的选择性机理:当水合Ca~(2+)和水合Mg~(2+)靠近Ca~(2+)-ATP酶时,酶-水界面上的蛋白空穴会优先结合Mg~(2+),导致Mg~(2+)的浓度在局部区域内降低,而这时游离的Ca~(2+)就相对较多。即使有键合的Ca~(2+),其与配体之间较弱的结合力也会使得它们很容易被释放,因此Ca~(2+)可以相对容易地进入Ca~(2+)-ATP酶中的离子传输通道。对于极少数随Ca~(2+)进入通道的Mg~(2+),配体对于Mg~(2+)的强亲合阻止了这个离子的自由传导,而结合较弱的Ca~(2+)则可以以较高的速率通过Ca~(2+)-ATP酶的跨膜区域。此现象与以前报导的“sticky-pore”假说相一致。另外一个影响Ca~(2+)和Mg~(2+)选择性的因素是结合位点空穴的大小和结合位点处的配体在结合阳离子时所能提供的配位数。研究发现,在高亲和位点Ⅰ和Ⅱ处,位点空穴大小和结合位点处的七配位特征更有利于Ca~(2+)的耦合。对于价态不同的Na~+、K~+和Ca~(2+),有如下的几个离子选择性机理(以Na~+和Ca~(2+)为例):第一,一个Ca~(2+)和两个Na~+拥有相同的电荷中和能力,却占有更小的空间,同时由于通道狭小的空间,更倾向于结合Ca~(2+);第二,在传导过程中,若有Na~+、K~+占据配位点,由于Ca~(2+)与配体有更强的相互作用,它可以很容易地取代一价离子,从而占据配位点。第三,配位点处的配体耦合数不适于Na~+的结合。
非键结合模式在钙离子传导过程中的作用非键作用在生命体中广泛存在,而其中的阳离子-π耦合模式在Ca~(2+)-ATP酶、K~+通道和季铵盐通道抑制剂等方面都有重要的作用。因此,我们用二阶微扰的方法计算了与肌质网钙泵和钙通道相关的Ca~(2+)-π相互作用和脂肪族氨基酸参与的Ca~(2+)-π相互作用。计算结果表明,芳香性分子所具有的离域π键特征使得它们成为结合Ca~(2+)的良好配体。而脂肪族氨基酸边链参与反应之后,可以极大地提高Ca~(2+)-配体之间的作用强度。具体来说,对于Ca~(2+)-π复合物,我们研究了Ca~(2+)分别与一到三个苯分子的耦合特征。当Ca~(2+)与两个苯环相互作用时,所对应的最低能量构型是一个交错平行的三明治结构;而当Ca~(2+)与三个苯环作用时,所对应的最低能量构型是一个笼状的结构。很明显,这些结构都具有最小的配体排斥力,并且能够有效地稳定复合物体系。同样的现象也发生在甲酰胺和乙酸耦合的Ca~(2+)-π复合物中。值得注意的是,当甲酰胺直接与苯分子结合时,它对苯环的芳香性特征几乎没有什么影响,而乙酸与苯环的结合则会削弱苯环的芳香性特征。这一点可以从NBO分析和键合轨道分析中反映出来。本章计算结果所体现的最重要的一点是:与脂肪族边链相比,芳香族边链对Ca~(2+)的结合能力更小。而在与肌质网相关的Ca~(2+)传导过程中,达到结合-释放平衡是非常重要的。芳香性分子对Ca~(2+)更弱的亲合使得Ca~(2+)可以更容易从结合的配体中释放出来,从而达到结合-释放的微妙平衡。因此,我们认为芳香性氨基酸在Ca~(2+)传导过程中应该起到了重要的作用。除此之外,Ca~(2+)的结合可以减小蛋白配体的HUMO-LUMO能差,从而导致荧光现象的发生。这一点可以为实验学家们研究Ca~(2+)的结合位点和传导过程提供理论信息和帮助。
In skeletal muscle,the calcium ions transport against a concentration gradient from the cytoplasm into the sarcoplasmic reticulum by Ca~(2+)pump and Ca~(2+)-channel, which can control the muscles' contraction and the heat production.In addition,the activity of the Ca~(2+)conductivity can signal the metabolism of various cells efficiently. Thus the maladjustment of the Ca~(2+)pump would result in many diseases and the corresponding work must be done as soon as possible.By now,the mechanism of the Ca~(2+)pump and Ca~(2+)-channel remains ambiguous.Thus,in the present doctoral dissertation,the relative studies on the geometrical changes,energetic transmission, and the coupling mechanisms between Ca~(2+)ions and the main active sites of Ca~(2+) pump have been systematically and extensively investigated employing the theoretical chemistry menthods.Additionally,the specificity and selectivity of Ca~(2+)have also be studied to explore the functions and interactive essence of the Ca~(2+)pump and Ca~(2+)-channel.Besides,the environmental factors,such as the peripheral amino acid and solvent effects,have also been investigated.Upon these studies,the corresponding mechanical models and thermodynamics parameters to describe the Ca~(2+)transport have been established elaborately.As a result,some significant progresses have been made,which can be described as follows.
(?)Coupling Character Between the Acidic Amino Acid Residues and Ca~(2+)and the Corresponding Biological Implicaitons Among the amino acid residues in the sarcoplasmic reticulum(SR)Ca~(2+)-ATPase,glutamic acid has played the important roles on the process of the Ca~(2+)transmembrane conductivity.On one hand,it paricipates the Ca~(2+)coupling in the high-affinity sites;and on the other hand,it is likely to be able to "sense" if siteⅡis occupied by Ca~(2+).So,glutamic acid could be part of the Ca~(2+)channel.In the present doctoral dissertation,we have investigated the biological relevant glutamic acid-Ca~(2+)bonding with density functional theory calculations.Sixteen chelating modes,which are divided into three different chelating types,that is,tridentate,bidentate,and monodentate forms,have been found.Among these isomers,the lowest energy structure is a zwitterionic form,
corresponding to Ca~(2+)interacting with three carbonyl oxygen atoms.Another tridentate form,with a bonding property of the calcium cation interacting with two carbonyl oxygen atoms and one amino nitrogen,is only 2.1 kcal/mol higher in energy. The geometrical character and relative stability of all isomers have been analyzed from the aspects of coupling forms,relative energies,electrostatic interactions, deformation energies,charge distributions,bonding characters,and intramolecular H-bonds.Results indicate that,among three active groups in glutamic acid,the binding ability order is the carbonyl O＞the amino N＞the hydroxyl O,and the main binding character is that Ca~(2+)couples with glutamic acid as in the multidentate form as possible.Became of the similarity in geometry and energy,the geometric transformation mechanisms among different structures have been explored.In actual biological processes of Ca~(2+)transport,the residues around Ca~(2+)have undergone conformational changes,which can be partly explained by our research:when Ca~(2+) binds to the high-affinity binding sites of El conformation of SR Ca~(2+)-ATPase,the glutamic acid chelates with Ca~(2+)in a stable form like the tri- or bidentate forms;but when Ca~(2+)-ATPase changes to the low-affinity conformation,the glutamic acid-Ca~(2+) chelate is in an unstable form,such as the monodentate geometry,thus release the calcium cation easily.Moreover,harmonic vibrational frequencies and their corresponding infrared frequencies have been determined for chelates in the gas-phase employing the B3LYP/6-31+G(d,p)level of theory.The frequency analyses indicate that the biggest vibratioanl intensity peak corresponds to the C=O stretching mode and it is red-shifted after it binds with Ca~(2+).
(?)Effects of the Stepwise Hydration on the Glutamic Acid-Ca~(2+)
Complexes and the Corresponding Biological Implicaitons In vivo,the complexes exist in the bulk solvent.Considering the effect of water,some different phenomena may take place for the glutamic acid-Ca~(2+)complexes.To approach the real biological processes,the stepwise hydration effects on the glutamic acid-Ca~(2+) complexes have been investigated systematically by employing the B3LYP density functional theory method with the 6-31+G(d,p)and 6-311++G(2d,p)basis sets.The thermodynamics parameters for the hydration reactions,the stepwise hydration energies,and accurate geometries have been explored.To elucidate the Ca~(2+)-ligand interaction,the charge transfer,bonding analysis,and IR spectroscopic characteristics have also been investigated.The calculated resultes have revealed that the stepwise hydration has caused a series of geometrical changes on the glutamic acid-Ca~(2+) complexes.Influenced by the ion-ligand electrostatic interaction,charge transfer from ligand to ion,electronic orbital effects,ion-ligand and ligand-ligand repulsions,the increase of the water molecules in the first shell has weakened the Ca~(2+)-O bond strength,which also results in the decrease of the(C-)O-Ca~(2+)-O(-C)bond angles. Notably,in the first-and-second-shell coordination mode,the peripheral hydration has caused the calcium cation to move closer to the first-shell water molecules,but increased the distance between Ca~(2+)and the carboxylic oxygen atoms.Additionally, because of the increase of the H-bonds,the stepwise hydration has stabilized the glutamic acid-Ca~(2+)complexes.The correlating data have shown that all of the stepwise hydration reactions are enthalpy-driven because of the relatively small value of△S,but the number of coordinated water molecules in the first shell of Ca~(2+)is not limitless.In our study,the optimal coordination number(CN)of Ca~(2+)in the first shell is 6 or 7;the former value agrees well with the datum reported in the Protein Data Bank(PDB),and the latter is the reflection of the most frequent Ca~(2+)-binding motif, EF-hand,in soluble proteins.Furthermore,the self-consistent reaction field(SCRF) and higher-level MP2 calculations have confirmed our conclusions.Additionally and very importantly,the stepwise hydration in either the first or second coordination shell can weaken the glutamic acid-Ca~(2+)interaction gradually till the glutamic acid ligand is replaced by the added water molecules,resulting in the conversion of coordination mode of the glutamic acid to Ca~(2+)from the inner-sphere one to a peripheral interaction mode,just like the ligand exchange process in the Ca~(2+)release channel existing in the real biological system.Finally,the similarities and discrepancies between our model and the Ca~(2+)-channel in vivo have been compared.
(?)Essence of the Ion Selectivity and the Influence Factors As reported previously,the SR Ca~(2+)-ATPase selectively transports Ca~(2+)in the presence of 10~3-10~5=fold higher concentrations of Mg~(2+).However,the selective mechanisms of the Ca~(2+)-ATPase to the calcium ions against the magnesium ions remain ambiguous, and much fewer studies on the basis of the physicochemical characteristics have been reported.Thus,we investigated the nature of the different amino acid residues interacting with the biologically active Ca~(2+)and Mg~(2+)and the selective transportation of Ca~(2+)over Mg~(2+)at the enzyme-water interface and in the entrance channel of the SR Ca~(2+)-ATPase.The calculated results demonstrate that the electronegative protein cavities,composed of either aliphatic or aromatic amino acids,at the enzyme-water interface and in the entrance channel prefer to bind Mg~(2+)rather than Ca~(2+)due to the stronger electrostatic interactions between Mg~(2+)and ligands.Further investigations show that the affinities of amino acids to the hydrated cations depend on the nature of the metal cations and the electronegativity and binding mode(the first- vs second=shell binding;mono-vs bidentate binding)of the amino acid ligands.In detail, relative to Ca~(2+),Mg~(2+)has a stronger electrostatic interaction to the same ligands because of its smaller radius and bigger charge density.On the other hand,when the electronegativity of the ligand increases,the ligand exhibits a bigger affinity to Mg~(2+). Simultaneously,discrimination of the ligands between Ca~(2+)and Mg~(2+)is also enhanced.For the studied cases,the order of the ligand discrimination between Ca~(2+) and Mg~(2+)are as follows:Trp-Glu＞Trp-Gln＞Trp-Trp＞Trp.In addition,the ligand binding modes have essential effects on ligand discrimination.In the Trp and Trp-Trp cases reactions with the biggest ion-selectivity are those which exhibit the second-shell indole binding,while for the Trp-Gln and Trp-Glu cases reactions with the biggest ion selectivity are those whose products have the second-shell indole and the first-shell monodentate aliphatic amino acids.More importantly,the calculations supplied feasible mechanisms to explain the size selectivity of Ca~(2+)over Mg~(2+). Concretely to say,when these two kinds of hydrated cations move to the vicinity of the SR Ca~(2+)-ATPase,the protein pockets at the enzyme-water interface bind Mg~(2+) more tightly than Ca~(2+),resulting in the concentration decrease of Mg~(2+)in the local region.Then Ca~(2+)transports into the entrance channel of the Ca~(2+)=ATPase favorably. As for the few Mg~(2+)ions,which may go into the entrance channel accompanying the Ca~(2+)current,the big affinity of the ligands to Mg~(2+)hampered the transportation of this cation freely,so the incompactly bound Ca~(2+)can transport through the transmembrane region of the Ca~(2+)-ATPase at a relatively high rate.This phenomenon is consistent with the "sticky-pore" hypothesis reported previously.Other very important factors to distinguish Ca~(2+)and Mg~(2+)are the size of the cavities formed by the binding sites and the preferred coordination number of these two cations. Additionally,the phenomenon of Ca~(2+)selectivity against much higher background concentrations of monovalent Na~+ and K~+ can be explainded as follows(take Na~+ for example):Firstly,Ca~(2+)ions have the same charge-neutralizing effect as two Na~+ ions while occupying less of the limited volume of the filter.Secondly,because the divalent calcium ions are more strongly attracted by the channel they can displace the sodium ions to occupy this region.Once there,Ca~(2+)can only be moved by the repulsion from another divalent ion and not by the lower repulsion from Na~+.Thirdly, the preferred coordination number of Na~+(6)and the average Na~+-O bond length (2.40(?))are unmatched to the Ca~(2+)channel.
(?)Effects of the Ca~(2+)-πNonvalent Interactions on the Ca~(2+)Transfer Nonvalent interactions exist in the biological processes extensively.Among them, cation-πinteraction has played the important roles in the Ca~(2+)-ATPase,K~+ channels, and quaternary ammonium inhibitors.Thus,we have studied the biologically relevant Ca~(2+)-πinteractions and aliphatic amino acid coupled Ca~(2+)-πinteractions by the Moller-Plesset calculations.The calculated results indicated that the delocalizedπcharacteristics make the aromatic molecules the active ligands to bind Ca~(2+). Furthermore,the participations of the side chains of the aliphatic amino acids enhanced the Ca~(2+)-ligands interactions greatly.For the Ca~(2+)-πcomplexes,we have investigated how Ca~(2+)bind to one up to three benzene molecules.When Ca~(2+)interacts with two benzene rings,the lowest energy structure is a staggered-parallel sandwich (SPS)form;while when Ca~(2+)interacts with three benznene molecules,the lowest energy structure corresponds to a caged(C)form.Inevitably,these cases have the smallest ligands repulsions,which can stabilize the systems effectively.The same phenomena occur in the formamide- and acetate-coupled Ca~(2+)-πcomplexes.Notably, when formamide binds the benzene molecule directly,it has few effect on the aromatic characteristics of benzene.In contrast,the binding of acetate to the benzene ring will weaken the aromatic characteristics of benzene,which can be verified by the NBO and orbital analyses.Most importantly,our calculations have revealed that the side chains of the aliphatic amino acids bind Ca~(2+)more strongly than those of the aromatic amino acids.Considerably,the weaker affinity of the aromatic iigands to Ca~(2+)has resulted in the easier desorption of this cation from the ligands.Thus the aromatic amino acids can play the important roles in the binding-release balance of Ca~(2+)in the Ca~(2+)-ATPase.In addition,the Ca~(2+)binding can reduce the HUMO-LUMO gaps of the protein ligands,resulting in the occurance of the fluorescence,which may be useful for the experimentalists to detect the Ca~(2+)binding sites and conductivity processes.
引文
[1]Advanced information on the Nobel Prize in Chemistry.[J].THE ROYAL SWEDISH ACADEMY OF SCIENCES.8 October 2003.
[2]刘宣良:林进中:陈锦文.二零零三年诺贝尔化学奖[J].科学发展.2004,376,59-63.
[3](a)Toyoshima,C.;Nomura,H.Structural changes in the calcium pump accompanying the dissociation of calcium[J].Nature 2002,418,605-611.
(b)Toyoshima,C.;Nomura,H.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution[J].Nature 2000,405,647-655.
(c)Toyoshima,C.;Mizutani,T.Crystal structure of the calcium pump with a bound ATP analogue[J].Nature 2004,430,529-536.
(d)Toyoshima,C.;Nomura,H.;Tsuda,T Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues[J].Nature 2004,432,361-368.
(e)Obara,K.;Miyashita,N.;Xu,C.;Toyoshima,I.;Sugita,Y.;Inesi,G.;Toyoshima,C.Structural role of countertransport revealed in Ca~(2+)pump crystal structure in the absence of Ca~(2+)[J].Prec.Natl.Acad.Sci.USA 2005,102,14489-14496.
(f)Takahashi,M.;Kondou,Y;Toyoshima,C.Interdomain communication in calcium pump as revealed in the crystal structures with transmembrane inhibitors [J].Prec.Natl.Acad.Sci.USA 2007,104,5800-5805.
[4]Sorensen,T.L.;Moiler,J.V.;Nissen,P.Phosphoryl Transfer and Calcium Ion Occlusion in the Calcium Pump[J].Science 2004,304,1672-1675.
[5](a)Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
(b)Lee,A.G.A calcium pump made visible[J].Curr.Opin.Struct.Biol.2002,12,547-554.
[6]Xu,C.;Rice,W.J.;He,W.;Stokes,D.L.A structural modal for the catalytic cycle of Ca~(2+)-ATPase[J].J.Mol.Biol.2002,316,201-211.
[7]Ostwald,W.Elektrische Eigenschaften halbdurchlassiger Scheidewande[J].Z.Phys.Chem.1890,6,71-82.
[8]Michaelis,L.Contribution to the theory of permeability of membranes for electrolytes[J].J.Gen.Physiol.1925,8,33-59.
[9]Hodgkin,A.L.The ionic basis of nerve conduction.In Nobel Lectures in Physiology or Medicine 1963-1970,Amsterdam,Elsevier Publishing Company.1970.
[10]Huxley,A.F.The quanataive analysis of excitation and conduction in nerve.In Nobel Lectures in Physiology or Medicine 1963-1970,Amsterdam,Elsevier Publishing Company.1970.
[11]Doyle,D.;Cabral,J.;Pfuetzner,R.;Kuo,A.;Gulbis,J.;Cohen,S.;Chait,B.;MacKinnon,R.The structure of the potassium channel:Molecular basis of K~+conduction and sensitivity[J].Science 1998,280,69-77.
[12]Jiang,Y.;Lee,A.;Chen,J.;Cadene,M.;Chait,B.T.;MacKinnon,R.Crystal structure and mechanism of a calcium-gated potassium channel[J].Nature 2002a,417,515-522.
[13](a)Buoninsegni,F.T.;Bartolommei,G.;Moncelli,M.;Inesi,G.;Guidelli,R.Time-Resolved Charge Translocation by Sarcoplasmic Reticulum Ca~(2+)-ATPase Measured on a Solid Supported Membrane[J].Biophys.J.2004,86,3671-3686.
(b)Salvador,J.M.;Inesi,G.;Rigaud,J.-L.,Mata,A.M.Ca~(2+)Transport by Reconstituted Synaptosomal ATPase Is Associated with H~+ Countertransport and Net Charge Displacement[J].J.Biol.Chem.1998,273,18230-18234.
(c)Yu,X.;Carroll,S.;Rigaud,J.-L.;Inesi,G H~+ countertransport and electrogenicity of the sarcoplasmic reticulum Ca~(2+)pump in reconstituted proteoliposomes.[J].Biophys.J.1993,64,1232-1242.
(d)Zhang,Z.;Lewis,D.;Strock,C.;Inesi,G.Detailed Characterization of the Cooperative Mechanism of Ca~(2+)Binding and Catalytic Activation in the Ca~(2+)Transport(SERCA)ATPase[J].Biochemistry 2000,39,8758-8767.
[14](a)Drake,S.K.;Lee,K.L.;Falke,J.J.Tuning the equilibrium ion affinity and selectivity of the EF-hand calcium binding motif:Substitutions at the gateway positions[J].Biochemistry 1996,35,6697-6075.
(b)Falke,J.J.;Drake,S.K.;Hazard,A.L.;Peersen,O.B.Molecular tuning of ion binding to calcium signaling proteins[J].Q.Rev.Biophys.1994,27,219-290.
(c)Drake,S.K.; Zimmer,M.A.;Kundrot,C.;Falke,J.J.Molecular Tuning of an EF-Hand-like Calcium Binding Loop.Contributions of the Coordinating Side Chain at Loop Position 3[J].J.Gen.Physiol.1997,110,173-184.
(d)Drake,S.K.;Zirnmer,M.A.;Miller,C.L.;Falke,J.J.Optimizing the metal binding parameters of an EF-hand-like calcium chelation loop:Coordinating side chains play a more important tuning role than chelation loop flexibility[J].Biochemislry 1997,36,9917-9926.
[15]Sugita,Y.;Miyashita,N.;Ikeguchi,M.;Kidera,A.;Toyoshima,C.Protonation of the Acidic Residues in the Transmembrane Cation-Binding Sites of the Ca~(2+)Pump[J].J.Am.Chem.Soc.2005,127,6150-6151.
[16]Costa,V.;Carloni,P.Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca~(2+)-ATPase:Insights from molecular modeling[J].Proteins:Struct.,Funct.,Genet..2003,50,104-113.
[17]Dudev,T.;Lim,C.Effect of carboxylate-bindmg mode on metal binding and electivity in proteins[J].Acc.Chem.Res.2007,40,85-93.
[18]朱维良;蒋华良;陈凯先;嵇汝运;曹阳.分子间相互作用的量子化学研究方法[J].化学进展 1999,11,247-253.
[1]Lee,A.G.A calcium pump made visible[J].Curr.Opin.Struct.Biol.2002,12,547-554.
[2]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reficulun at 2.6A resolution[J].Nature 2000,405,647-655.
[3]Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
[4](a)Inesi,G.Sequential mechanism of calcium binding and translocation in sarcoplasmic reticulum adenosine triphosphatase[J].J.Biol.Chem.1987,262,16338-16342;
(b)de Meis,L.The Sarcoplasmic Reticulum:Transport and Energy Transduction,Wiley,New York 1981,2,1-163.
[5]Sun,W.;Kinsel,G.R.;Matynick,D.S.Computational Estimates of the Gas-Phase Basicity and Proton Affinity of Glutamic Acid[J].J.Phys.Chem.A 1999,103,4113-4117.
[6]Moussatova,A.;Vazquez,M.-V.;Martinez,A.;Dolgounitcheva,O.;Zakrzewski,V.G.;Ortiz,J.V.;Pedersen,D.B.;Simard,B.Theoretical Study of the Structure and Bonding of a Metal-DNA Base Complex:Al-Guanine[J].J.Phys.Chem.A 2003,107,9415-9421.
[7]Jensen,F.Structure and stability of complexes of glycine and glycine methyl analogs with H~+,Li~+,and Na~+[J].J.Am.Chem.Soc.1992,114,9533-9537.
[8]Russo,N.;Toscano,M.;Grand,A.Bond Energies and Attachments Sites of Sodium and Potassium Cations to DNA and RNA Nucleic Acid[J].J.Am.Chem.Soc.2001,123,10272-10279.
[9]Russo,N.;Toscano,M.;Grand,A.Gas-Phase Absolute Ca~(2+)and Mg~(2+)Affinity for Nucleic Acid Bases.A Theoretical Determination[J].J.Phys.Chem.A 2003,107,11533-11538.
[10]Hoyau,S.;Ohanessian,G.Absolute Affinities of α-Amino Acids for Cu~+ in the Gas Phase.ATheoretical Study[J].J.Am.Chem.Soc.1997,119,2016-2024.
[11]Bertran,J.,Rodriguez-Santiago,L.;Sodupe,M.The Different Nature of Bonding in Cu~+-Glycme and Cu~(2+)-Glyclne[J].J.Phys.Chem.B 1999,103,2310-2317.
[12]Marine,T.;Russo,N.,Toscano,M.Gas-phase metal ion(Li~+,Na~+,Cu~+)affinities of glycine and alanine[J].J Inorg.Biochem.2000,79.179-185.
[13]Remko,M.;Rode,B.M.Bivalent cation binding effect on formation of the peptide bond[J].Chem.Phys.Lett.2000,316,489-494.
[14]Moision,R.M.,Armentrout,P.B.Experimental and Theoretical Dissection of Sodium Cation/Glycine Interactions[J].J Phys.Chem.A 2002,106,10350-10362.
[15]Ai,H.;Bu,Y.;Li,P.Intramolecular proton transfer induced by divalent alkali earth metal cation in the gas state[J].Int.J Quantum.Chem.2003,94,205-214.
[16]Corral,I.;Me,O.;Yanez,M.;Scott,A.P.;Radom,L.Interactions between Neutral Molecules and Ca~(2+):An Assessment of Theoretical Procedures[J].J Phys.Chem.A 2003,107,10456-10461.
[17]Dunbar,R.C.Complexation of Na~+ and K~+ to Aromatic Amino Acids:A Density Functional Computational Study of Cation-π Interactions[J].J Phys.Chem.A 2000,104,8067-8074.
[18]Tsipis,A.C.;Tsipis,C.A.;Valla,V.Quantum chemical study of the coordination of glycolic acid conformers and their conjugate bases to[Ca(OH_2)_n]~(2+)(n=0-4)ions[J].J Mol.Struct.(Theochem.)2003,630,81-100.
[19](a)Bouchonet,S.;Hoppilliard,Y.Proton and sodium ion affinities of glvcine and its sodium salt in the gas phase.Ab initio calculations[J].Org.Mass Spectrom.1992,27,71-76.
(b)Bouchonet,S.;Flament,J.P.;Hoppilliard,Y.Desorption-ionization and in-flight fragmentation of monoalkali-glycine adducts:Plasma-desorption mass spectrometry and Ab initio calculations[J].Rapid Commun.Mass Spectrom.1993,7,470-476.
[20]Hoyau,S.;Ohanessian,G Interaction of Alkali Metal Cations(Li~+-Cs~+)with Glycine in the Gas Phase:A Theoretical Study[J].Chem.Eur.J.1998,4,1561-1569.
[21]Wyttenbach,T.;Witt,M.;Bowers,M.T.On the Stability of Amino Acid Zwitterions in the Gas Phase:The Influence of Derivatization,Proton Affinity,and Alkali Ion Addition[J].J.Am.Chem.Soc.2000,122,3458-3464.
[22]Pulkkinen,S.;Noguera,M.;Rodriguez-Santiago,L.;Sodupe,M.;Bertran,J.Gas Phase Intramolecular Proton Transfer in Cationized Glycine and Chlorine Substituted Derivatives(M-Gly,M=Na~+,Mg~(2+),Cu~+,Ni~+,and Cu~(2+)):Existence of Zwitterionic Structures?[J].Chem.Eur.J.2000,6,4393-4399.
[23]Strittmatter,E.F.;Lemoff,A.S.;Williams,E.R.Structure of Cationized Glycine,Gly·M~(2+)(M=Be,Mg,Ca,Sr,Ba),in the Gas Phase:Intrinsic Effect of Cation Size on Zwitterion Stability[J].J.Phys.Chem.A 2000,104,9793-9796.
[24]Rulisek,L.;Havlas,Z.Theoretical Studies of Metal Ion Selectivity.1.DFT Calculations of Interaction Energies of Amino Acid Side Chains with Selected Transition Metal Ions(Co~(2+),Ni~(2+),Cu~(2+),Zn~(2+),Cd~(2+),and Hg~(2+))[J].J.Am.Chem.Soc.2000,122,10428-10439.
[25](a)Becke,A.D.Density-functional thermochemistry.Ⅲ.The role of exact exchange[J].J.Chem.Phys.1993,98,5648-5652.
(b)Lee,C.;Yang,W.;Parr,R.G.Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density[J].Phys.ReV.B 1988,37,785-789.
(c)Stevens,P.J.;Devlin,F.J.;Chablowski,C.F.;Frisch,M.J.Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force[J].J.Phys.Chem.1994,98,11623-11627.
[26]Dudev,T.;Lim,C.Monodentate versus Bidentate Carboxylate Binding in Magnesium and Calcium Proteins:What Are the Basic Principles?[J].J.Phys.Chem.B 2004,108,4546-4557.
[27]Ban,F.;Kusalik,P.;Weaver,D.F.Density Functional Theory Investigations on the Chemical Basis of the Selectivity Filter in the K~+ Channel Protein[J].J.Am.Chem.Soc.2004,126,4711-4716.
[28]Frisch,M.J.;Del Bene,J.E.;Binkley,J.S.;Schaefer,H.F.,Ⅲ.Extensive theoretical studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[29]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press: Cleveland,82nd edn,2001-2002.
[30]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.;Chen,W.;Wong,M.W.,Andres,J.L.;Gonzalez,C.;Head-Gordon,M.;Replogle,E.S.;Pople,J.A.Gaussian 98,Revision A.9;Gaussian,Inc.;Pittsburgh PA,1998.
[1]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6A resolution[J].Nature 2000,405,647-655.
[2](a)Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683;
(b)Lee,A.G.A calcium pump made visible[J].Curr.Opin.Struct.Biol.2002,12,547-554.
[3]Xu,C.;Rice,W.J.;He,W.;Stokes,D.L.A structural modal for the catalytic cycle of Ca~(2+)-ATPase[J].J Mol.Biol.2002,316,201-211.
[4]Sorensen,T.L.;Moiler,J.V.;Nissen,P.Phosphoryl Transfer and Calcium Ion Occlusion in the Calcium Pump[J].Science 2004,304,1672-1675.
[5]Costa,V.;Carloni,P.Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca~(2+)-ATPase:Insights from molecular modeling[J].Proteins:Struct.,Funct.,Genet..2003,50,104-113.
[6](a)Dudev,T;Lim,C.Monodentate versus Bidentate Carboxylate Binding in Magnesium and Calcium Proteins:What Are the Basic Principles?[J].J.Phys.Chem.B 2004,108,4546-4557;
(b)Babu,C.S.;Dudev,T.;Casareno,R.;Cowan,J.A.;Lim,C.A Combined Experimental and Theoretical Study of Divalent Metal Ion Selectivity and Function in Proteins:Application to E.coli Ribonuclease H1[J].J.Am.Chem.Soc.2003,125,9318-9328;
(c)Dudev,T.;Lin,Y.L.;Dudev,M.;Lira,C.First-Second Shell Interactions in Metal Binding Sites in Proteins:A PDB Survey and DFT/CDM Calculations[J].J.Am.Chem.Soc.2003,125,3168-3180;
(d)Dudev,T.;Lim,C.Principles Governing Mg,Ca,and Zn Binding and Selectivity in Proteins[J].Chem.Rev.2003,103,773-788;
(e)Dudev,T.;Lim,C.A DFT/CDM Study of Metal-Carboxylate Interactions in Metalloproteins:Factors Governing the Maximum Number of Metal-Bound Carboxylates[J].J Am.Chem.Soc.2006,128,1553-1561.
[7]Xiang,F.;Bu,Y.;Ai,H.;Li,P.The Coupling Character of Ca~(2+)with Glutamic Acid:Implication for the Conformational Behavior and Transformation of Ca~(2+)-ATPase in Transmembrane Ca~(2+)Channel[J].J.Phys.Chem.B 2004,108,17628-17638.
[8]Jockusch,R.A.;Lemoff,A.S.;Williams,E.R.Hydration of Valine-Cation Complexes in the Gas Phase:On the Number of Water Molecules Necessary to Form a Zwitterion[J].J.Phys.Chem.A 2001,105,10929-10942.
[9]Carrell,C.J.;Carrell,H.L.;Erlebacher,J.;Glusker,J.P.Structural aspects of metal ion carboxylate interactions[J].J.Am.Chem.Soc.1988,110,8651-8656.
[10]Tiraboschi,G.;Roques,B.;Gresh,N.Joint quantum chemical and polarizable molecular mechanics investigation of formate complexes with penta- and hexahydrated Zn~(2+):Comparison between energeties of model bidentate,monodentate,and through-water Zn~(2+)binding modes and evaluation of nonadditivity effects[J].J.Comput.Chem.1999,20,1379-1390.
[11]Abola,E.E.;Sussman,J.L.;Prilusky,J.;Manning,N.O.Protein Data Bank archives of three-dimensional macromolecular structures.[J].Methods Enzymol.1997,277,556-571.
[12]Yang,W.;Jones,L.M.;Isley,L.;Ye,Y.;Lee,H.-W.;Wilkins,A.;Liu,Z.;Hellinga,H.W.;Malchow,R.;Ghazi,M.;Yang,J.J.Rational Design of a Calcium-Binding Protein[J].J.Am.Chem.Soc.2003,125,6165-6171.
[13]Pidcock,E.;Moore,G.R.Structural characteristics of protein binding sites for calcium and lanthanide ions[J].J.Biol.Inorg.Chem.2001,6,479-489.
[14]Sugita,Y.;Miyashita,N.;Ikeguchi,M.;Kidera,A.;Toyoshima,C.Protonation of the Acidic Residues in the Transmembrane Cation-Binding Sites of the Ca~(2+)Pump [J].J.Am.Chem.Soc.2005,127,6150-6151.
[15]Bernal-Uruchurtu,M.I.;Ortega-Blake,I.A refined Monte Carlo study of Mg~(2+)and Ca~(2+)hydration[J].J.Chem.Phys.1995,103,1588-1598.
[16](a)Becke,A.D.Density-functional thermochemistry.Ⅲ.The role of exact exchange[J].J.Chem.Phys.1993,98,5648-5652;
(b)Lee,C.;Yang,W.;Parr,R.G.Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density[J].Phys.Rev.B 1988,37,785-789;
(c)Stevens,P.J.;Devlin,F.J.;Chablowski,C.F.;Frisch,M.J.Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields[J].J.Phys.Chem.1994,98,11623-11627.
[17]Peschke,M.;Blades,A.T.;Kebarle,P.Binding Energies for Doubly-Charged Ions M~(2+)=Mg~(2+),Ca~(2+)and Zn~(2+)with the Ligands L=H_2O,Acetone and N-methylacetamide m Complexes ML_n~(2+)for n=1 to 7 from Gas Phase Equilibria Determinations and Theoretical Calculations[J].J.Am.Chem.Soc.2000,122,10440-10449.
[18]Tsipis,A.C.;Tsipis,C.A.;Valla,V.Quantum chemical study of the coordination of glycolic acid conformers and their conjugate bases to [Ca(OH_2)_n]~(2+)(n=0-4)ions[J].J.Mol.Struct.(THEOCHEM)2003,630,81-100.
[19]Ai,H.;Bu,Y.Reservation Energy Bonds and Structural Stability of Series of Multihydrated(nine=1-10)Glycine-H~+M~+(M=Li,Na,or K)Complexes[J].J.Phys.Chem.B 2004,108,1241-1254.
[20]Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.K;Montgomery,J.A.;Vreven,Jr,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucci,B.;Cossi,M.;Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Adamo,C.;Jaramillo,J.;Gomperts,R.;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;PomeUi,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malick,D.K.;Rabuck,A.D.;Raghavachari,K.;Foresrnan,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Wong,W.Chen,;M.W.;Gonzalez,C.;Pople,J.A.GAUSSIAN 03(Revision B.05);Gaussian,Inc.,Pittsburgh,PA,2003.
[21]Frisch,M.J.;Bene,J.E.D.;Binkley,J.S.;Schaefer Ⅲ,H.F.Extensive theoretical studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[22]Cances,E.;Mennucci,B.;Tomasi,J.A new integral equation formalism for the polarizable continuum model:Theoretical background and applications to isotropic and anisotropie dielectrics[J].J.Chem.Phys.1997,107,3032-3041.
[23]Cossi,M.;Barone,V.;Mennucci,B.;Tomasi,J.Ab initio study of ionic solutions by a polarizable continuum dielectric model[J].Chem.Phys.Lett.1998,286,253-260.
[24]Mennucci,B.;Tomasi,J.Continuum solvation models:A new approach to the problem of solute's charge distribution and cavity boundaries[J].J.Chem.Phys.1997,106,5151-5158.
[25]Cossi,M.;Scalmani,G.;Rega,N.;Barone,V.New developments in the polarizable continuum model for quantum mechanical and classical calculations on molecules in solution[J].J.Chem.Phys.2002,117,43-54.
[26]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press:Cleveland,82nd edn,2001-2002.
[27]Corral,I.;Me,O.;Yanez,M.;Scott,A.P.;Radom,L.Interactions between Neutral Molecules and Ca~(2+):An Assessment of Theoretical Procedures[J].J.Phys.Chem.A 2003,107,10456-10461.
[1]Glynn,I.M.Annual review prize lecture.'All hands to the sodium pump'[J].J.Physiol.1993,462,1-30.
[2]Drake,S.K.;Lee,K.L.;Falke,J.J.Tuning the equilibrium ion affinity and selectivity of the EF-hand calcium binding motif:Substitutions at the gateway positions[J].Biochemistry 1996,35,6697-6075.
[3]Yau,W.M.;Wimley,W.C.;Gawrisch,K.;White,S.H.The Preference of Tryptophan for Membrane Interfaces[J].Biochemistry.1998,37,14713-14718.
[4]Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
[5]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticul[J].Nature 2000,405,647-655.
[6]Frontera,A.;Quinonero,D.;Garau,C.;Costa,A.;Ballester,P.;Deya,P.M.MP2 Study of Cation-(π)_n-π Interactions(n=1-4)[J].J.Phys.Chem.A 2006,110,9307-9309.
[7](a)Felder,C.;Jiang,H.;Zhu,W.;Chen,K.;Silman,I.;Botti,S.A.;Sussman,J.L.Quantum/Classical Mechanical Comparison of Cation-π Interactions between Tetramethylammonium and Benzene[J].J.Phys.Chem.A 2001,105,1326-1333.
(b)Liu,T.;Zhu,W.;Gu,J.;Shen,J.;Luo,X.;Chen,G.;Puah,C.M.;Silman,I.;Chen,K.;Sussman,J.L.;Jiang,H.Additivity of Cation-π Interactions:An ab Initio Computational Study on π-Cation-π Sandwich Complexes[J].J.Phys.Chem.A 2004,108,9400-9405.
(c)Tan.X.;Zhu,W.;Cui,M.;Luo,X.;Gu,J.;Silman,I.;Sussman,J.L.;Jiang,H.;Ji,R.;Chen,K.Spine high-throughput crystallization,crystal imaging and recognition techniques:current state,performance analysis,new technologies and future aspects[J].Chem.Phys.Lett.2001,349,113-1149.
[8](a)Dudev,T.;Lim,C.Effect of carboxylate-binding mode on metal binding and electivity in proteins[J].Acc.Chem.Res.2007,40,85-93.
(b)Dudev,T.;Lim,C.Competition between Protein Ligands and Cytoplasmic Inorganic Anions for the Metal Cation:A DFT/CDM Study[J].J.Am.Chem.Soc.2006,128,10541-10548.
[9]Jensen,F.Structure and stability of complexes of glycine and glycine methyl analogs with H~+,Li~+,and Na~+[J].J.Am.Chem.Soc.1992,114,9533-9537.
[10](a)Hoyau,S.;Ohanessian,G.Interaction of alkali metal cations(Li~+-Cs~+)with glycine in the gas phase:A theoretical study[J].Chem.Eur.J.1998,4,1561-1569.
(b)Hoyau,S.;Ohanessian,G.Absolute Affinities of α-Amino Acids for Cu~+ in the Gas Phase.A Theoretical Study[J].J.Am.Chem.Soc.1997,119,2016-2024.
[11]Wyttenbach,T.;Witt,M.;Bowers,M.T.On the question of salt bridges of cationized amino acids in the gas phase:glycine and arginine[J].Int.J.Mass Spectrom.2001,243,182-183.
[12]Pulkkinen,S.;Noguera,M.;Rodn'guez-Santiago,L.;Sodupe,M.;Bertran,J.Gas Phase Intramolecular Proton Transfer in Cationized Glycine and Chlorine Substituted Derivatives(M-Gly,M=Na~+,Mg~(2+),Cu~+,Ni~+,and Cu~(2+)):Existence of Zwitterionic Structures?[J].Chem.Eur.J.2000,6,4393-4399.
[13]Bertran,J.;Rodriguez-Santiago,L.;Sodupe,M.The Different Nature of Bonding in Cu~+-Glycine and Cu~(2+)-Glycine[J].J.Phys.Chem.B 1999,103,2310-2317.
[14]Ma,J.C.;Dougherty,D.The Cation-π Interaction[J].Chem.Rev.1997,97,1303-1324.
[15]Ryahov,V.;Dunbar,R.C.Interactions of Phenol and Indole with Metal Ions in the Gas Phase:Models For Tyr and Trp Side-Chain Binding[J].J.Am.Chem.Soc.1999,121,2259-2268.
[16]Jemigan,R.;Raghunathan,G.;Bahar,I.Characterization of.interactions and metal ion binding sites in proteins[J].Curr.Opin.Struct.Biol.1994,4,256-263.
[17]Gouaux,E.;MacKinnon,R.Principles of selective ion transport in channels and pumps[J].Science 2005,310,1461-1465.
[18]Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.R.;Montgomery,J.A.,Jr.;Vreven,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucci,B.;Cossi,M.; Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Bakken,V.;Adamo,C.;Jaramillo,J.;Gomperts,R;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;Pomelli,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malice D.K.;Rabuck,A.D.;Raghavachari,K.;Foresman,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Gonzalez,C.;Pople,J.A.Gaussian 03,revision B.05;Gaussian,Inc.:Wallingford,CT,2004.
[19](a)Becke,A.D.Density-functional thermochemistry.Ⅲ.The role of exact exchange[J].J.Chem.Phys.1993,98,5648-5652.
(b)Becke,A.D.Density-functional exchange-energy approximation with correct asymptotic behavior[J].Phys.Rev.1988,A38,3098-3104.
[20]Lee,C.;Yang,W.;Parr,R G.Development of the colle-salvetti correlation energy formula into a functional of the electron density[J].Phys.Rev.1988,B37,5-789.
[21]Becke,A.D.A new mixing of Hartree-Fock and local density-functional theories [J].J.Chem.Phys.1993,98,1372-1377.The BHandHLYP keyword in Gaussian employs a functional according to the formula,BHandHLYP:0.5×E_x(HF)+0.5×E_x(LSDA)+0.5×ΔE_x(Becke88)+E_c(LYP),which is not precisely the formulation proposed by A.D.Becke in his paper.
[22]Frisch,M.J.;Del Bene,J.E.;Binldey,J.S.;Schaefer,H.F.,Ⅲ.Extensive theoretical-studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[23](a)Glendening,E.D.;Reed,A.E.;Carpenter,J.E.;Weinhold,F.NBO Version 3.1,
(b)Reed,A.E.;Curtiss,L.A.;Weinhold,F.Intermolecular interactions from a natural bond orbital,donor-acceptor viewpoint[J].Chem.Rev.1988,88,899-926.
[24]Breneman,C.M.;Wiberg,K.B.Determining atom-centered monopoles from molecular electrostatic potentials.The need for high sampling density in formamide conformational analysis[J].J.Comp.Chem.1990,11,361-373.
[25]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press:Cleveland,82nd edn,2001-2002.
[26]Marcus,Y.Ionic radii in aqueous solutions[J].Chem.Rev.1988,88,1475-1498.
[27]Alabugin,I.V.;Manoharan,M.;Peabody,S.;Weinhold,F.Electronic Basis of Improper Hydrogen Bonding:A Subtle Balance of Hyperconjugation and Rehybridization[J].J.Am.Chem.Soc.2003,125,5973-5987.
[28]de Vos,A.M.;Ultshc,M.;Kossiakoff,A.A.American Chemistry in Context:Chemistry and Modem Society[J].Science 1992,255,306-312.
[29]Pflugrath,J.W.;Wigand,G.;Huber,R.;Vertesy,L.Crystal structure determination,refinement and the molecular model of the α-amylase inhibitor Hoe-467A[J].J Mol.Biol.1986,189,383-386.
[30]Rardin,R.L.;Tolmann,W.B.;Lippard,S.J.Monodentate carboxylate complexes and the carboxylate shift:implications for poly-metalloprotein structure and function[J].New J.Chem.1991,15,417-430.
[31]Rodriguez-Cruz,S.E.;Jockusch,R.A.;Williams,E.R.Binding Energies of Hexahydrated Alkaline Earth Metal Ions,M~(2+)(H_2O)_6,M=Mg,Ca,Sr,Ba:Evidence of Isomeric Struetures for Magnesium[J].J.Am.Chem.Soc.1999,121,1986-1987.
[32]Bezanilla,F.;Armstrong,C.M.Negative Conductance Caused by Entry of Sodium and Cesium Ions into the Potassium Channels of Squid Axons[J].J.Gen.Physiol.1972,60,588-608.
[33]Katz,A.K.;Glusker,J.P.;Beebe,S.A.;Bock,C.W.Calcium Ion Coordination:A Comparison with That of Beryllium,Magnesium,and Zinc[J].J.Am.Chem.Soc.1996,118,5752-5763.
[34](a)Falke,J.J.;Drake,S.K.;Hazard,A.L.;Peersen,O.B.Molecular tuning of ion binding to calcium signaling proteins[J].Q.Rev.Biophys.1994,27,219-290.
(b)Drake,S.K.;Zimmer,M.A.;Kundrot,C.;Falke,J.J.Molecular Tuning of an EF-Hand-like Calcium Binding Loop.Contributions ofthe Coordinating Side Chain at Loop Position 3[J].J.Gen.Physiol.1997,110,173-184.
(c)Drake,S.K.;Zimmer,M A.;Miller,C.L.;Falke,J.J.Optimizing the metal binding parameters of an EF-hand-like calcium chelation loop:Coordinating side chains play a more important tuning role than chelation loop flexibility[J].Biochemistry 1997,36,9917-9926.
[35]Nonner,W.;Catacuzzeno,L.;Eisenberg,B.Binding and selectivity in L-type calcium channels:a mean spherical approximation[J].Biophys.J.2000,79,1976-1992.
[36]Boda,D.;Busath,D.;Henderson,D.Sokolowski,S.Monte Carlo Simulations of the Mechanism for Channel Selectivity:The Competition between Volume Exclusion and Charge Neutrality[J].J.Phys.Chem.B 2000,104,8903-8910.
[37](a)Corry,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.A model of calcium channels[J].Biochim.Biophys.Acta 2000,1509,1-6.
(b)Corry,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.Mechanisms of permeation and selectivity in calcium channels[J].Biophys.J.2001,80,195-214.
(c)Corry,B.;Vora,T.;Chung,S.H.Electrostatic basis of valence selectivity in cationic channels[J].Biochim.Biophys.Acta 2005,1711,72-86.
(d)Corry,B.;Chung,S.H.Mechanisms of valence selectivity in biological ion channels[J].Cell.Mol.Life Sci.2006,63,301-315.
[38]Dudev,M.;Wang,J.;Dudev,T;Lim,C.Factors Governing the Metal Coordination Number in Metal Complexes from Cambridge Structural Database Analyses[J].J.Phys.Chem.B 2006,110,1889-1895.
[39]Dobler,M.Ionophores and Their Structures;Wiley:New York,1981.
[1]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticul[J].Nature 2000,405,647-655.
[2]Kohtani,M.;Jarrold,F.;Wee,S.;O'Hair R.A.J.Metal Ion Interactions with Polyalanine Peptides[J].J.Phys.Chem.B 2004,108,6093-6097.
[3]Dudev,T.;Lim,C.Effect of carboxylate-binding mode on metal binding and electivity in proteins[J].Acc.Chem.Res.2007,40,85-93.
[4](a)Xiang,F.;Bu,Y.;Ai,H.;Li,P.The Coupling Character of Ca~(2+)with Glutamic Acid:Implication for the Conformational Behavior and Transformation of Ca~(2+)-ATPase in Transmembrane Ca~(2+)Channel[J].J.Phys.Chem.B 2004,108,17628-17638.
(b)Xiang,F.;Li,P.;Yan,S.;Sun,L.;Cukier,R.;Bu,Y.Hydration effect on interaction mode between glutamic acid and Ca~(2+)and its biochemical implication:a theoretical explorationw[J].New J.Chem.2006,30,890-900.
(c)Xiang,F.;Cukier,R.I.;Bu,Y.Ca~(2+)Selectivity of the Sarcoplasmic Reticulum Ca~(2+)-ATPase at the Enzyme-Water Interface and in the Ca~(2+)Entrance Channel [J].J.Phys.Chem.B 2007,111,12282-12293.
[5]Kim,K.S.;Tarakeshwar,P.;Lee,J.Y.Molecular Clusters of-Systems:Theoretical Studies of Structures,Spectra,and Origin of Interaction Energies[J].Chem.Rev.2000,100,4145-4185
[6]Crowley,P.B.;Golovin,A.Cation-π Interactions in Protein-Protein Interfaces[J].Proteins:Struct.,Funct.,Genet.,2005,59,231-239
[7]Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
[8]Costa,V.;Carloni,P.Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca~(2+)-ATPase:Insights from molecular modeling[J].Proteins:Struct..Funct.,Genet.,2003,50,104-113.
[9]Huang,Y.;Bu,Y.Cooperative Dynamics Mechanism of Calcium Ions Binding to Sarcoplasmic Reticulum Ca~(2+)-ATPase:Insights from Molecular Dynamics Simulations[J].J.Phys.Chem.B(to be published)
[10]Gouaux,E.;MacKinnon,R.Principles of Selective Ion Transport in Channels and Pumps[J].Science 2005,310,1461-1465.
[11]Reddy,A.S.;Vijay,D.;Sastry,G.M.;Sastry,G.N.From Subtle to Substantial:Role of Metal Ions on π-π Interactions[J].J.Phys.Chem.B 2006,110,2479-2481
[12]Heginbotham,L.;MacKinnon,R.The aromatic binding site for tetraethylammonium ion on potassium channels[J].Neuron 1992,8,483-491.
[13](a)Doyle,A.D.;Cabral,M.J.;Pfuetzner,A.R.;Kuo,A.;Gulbis,M.J.;Cohen,L.S.;Chait,T.B.;MacKinnon,R.The Structure of the Potassium Channel:Molecular Basis of K~+ Conduction and Selectivity[J].Science 1998,280,69-77.
(b)French,J.R.;Shoukimas,J.J.Blockage of squid axon potassium conductance by internal tetra-N-alkylammonium ions of various sizes[J].Biophys.J.1981,34,271-291.
[14]Ma,J.C.;Dougherty,D.A.The Cation-π Interaction[J].Chem.Rev.1997,97,1303-1324.
[15]Coletti,C.;Re,N.Theoretical Study of Alkali Cation-Benzene Complexes:Potential Energy Surfaces and Binding Energies with Improved Results for Rubidium and Cesium[J].J.Phys.Chem.A 2006,110,6563-6570.
[16]Cheng,J.;Zhu,W.;Tang,Y.;Xu,Y.;Li,Z.;Chen,K.;Jiang,H.Effect of cation-π interaction on NMR:A theoretical investigation on complexes of Li~+,Na~+,Be~(2+),and Mg~(2+)with aromatics[J].Chem.Phys.Lett.2006,422,455-460.
[17]Felder,C.;Jiang,H.;Zhu,W.;Chen,K.;Silman,I.;Botti,S.A.;Sussman,J.L.Quantum/Classical Mechanical Comparison of Cation-π Interactions between Tetramethylammonium and Benzene[J].J.Phys.Chem.A 2001,105,1326-1333.
[18]Reddy,A.S.;Sastry,G.N.Cation[M=H~+,Li~+,Na~+,K~+,Ca~(2+),Mg~(2+),NH_4~+,and NMe_4~+]Interactions with the Aromatic Motifs of Naturally Occurring Amino Acids:A Theoretical Study[J].J.Phys.Chem.A 2005,109,8893-8903.
[19]Frontera,A.;Quinonero,D.;Garau,C.;Costa,A;BaUester,P.;Deya,P.M.MP2Study of Cation-(π)_n-π Interactions(n=1-4)[J].J.Phys.Chem.A 2006,110, 9307-9309.
[20]Li,H.;Boatz,J.A.;Gordon,M.S.Cation-Cation π-π Stacking in Small Ionic Clusters of 1,2,4-Triazolium[J].J.Am.Chem.Soc.2008,130,392-393.
[21]Ryzhov,V.;Dunbar,R.C.Interactions of Phenol and Indole with Metal Ions in the Gas Phase:Models For Tyr and Trp Side-Chain Binding[J].J.Am.Chem.Soc.1999,121,2259-2268
[22]Frisch,M.J.;Trucks,G.W.;Sehlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.R.;Montgomery,J.A.,Jr.;Vreven,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucei,B.;Cossi,M.;Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Bakken,V.;Adamo,C.;Jaramillo,J.;Gomperts,R.;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;Pomelli,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malick,D.K.;Rabuck,A.D.;Raghavaehari,K.;Foresman,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Gonzalez,C.;Pople,J.A.Gaussian 03,revision B.05;Gaussian,Inc.:Wallingford,CT,2004.
[23]Head-Gordon M.,Pople J.A.,Frisch M.J.MP2 energy evaluation by direct methods[J].Chem.Phys.Lett.1988,153,503-509.
[24]Rappe,A.K.;Bernstein,E.R.Ab Initio Calculation of Nonbonded Interactions:Are We There Yet?[J].J.Phys.Chem.A 2000,104,6117-6128.
[25]Frisch,M.J.;Bene,J.E.D.;Binkley,J.S.;Schaefer Ⅲ,H.F.Extensive theoretical studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[26](a)Glendening,E.D.;Reed,A.E.;Carpenter,J.E.;Weinhold,F.NBO Version 3.1,
(b)Reed,A.E.;Curtiss,L.A.;Weinhold,F.Intermolecular interactions from a natural bond orbital,donor-accepter viewpoint[J].Chem.Rev.1988,88,899-926.
[27]Breneman,C.M.;Wiberg,K.B.Determining atom-centered monopoles from molecular electrostatic potentials.The need for high sampling density in fotmamide conformational analysis[J].J.Comp.Chem.1990,11,361-373.
[28]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press:Cleveland,82nd edn,2001-2002.
[29]Tan.X.;Zhu,W.;Cui,M.;Luo,X.;Gu,J.;Silman,I.;Sussman,J.L.;Jiang,H.;Ji,R..;Chen,K.Spine high-throughput crystallization,crystal imaging and recognition techniques:current state,performance analysis,new technologies and future aspects[J].Chem.Phys.Lett.2001,349,113-1149.
[30]Reed,A.E.;Curtiss,L.A.;Weinhold,E;Intermolecular Interactions from a Natural Bond Orbital,Donor-Accepter Viewpoint[J].Chem.Rev.1988,88,899-926.
[31]Carpenter,J.E.;Weinhold,F.J.Mol.Struct.(Theochem.)Analysis of the geometry of the hydroxymethyl radical by the "different hybrids for different spins" natural bond orbital procedure[J].1988,169,41-62.
[32](a)Ratner,M.Electronic motion in DNA Nature,1999,397,480-481.
(b)Jortner,J.;Bixon,J.;Langenbacher,M.;Michel-Beryede,T.Charge transfer and transport in DNA[J].Prec.Natl.Acad.Sci.U.S.A.1998,95,12759-12765.
[33](a)Liu,H.;Gao,J.;Lynch,S.R.;Saito,Y.D.;Maynard,L.;Keel,E.T.A Four-Base Paired Genetic Helix with Expanded Size[J].Science 2003,302,868-871.
(b)Gao,J.;Liu,H.;Keel,E.T.Expanded-Size Bases in Naturally Sized DNA:Evaluation of Steric Effects in Watson-Crick Pairing[J].J.Am.Chem.Soc.2004,126,11826-11831.
(c)Liu,H.;Gao,J.;Keel,E.T.Helix-Forming Properties of Size-Expanded DNA,an Alternative Four-Base Genetic Form[J].J.Am.Chem.Soc.2005,127,1396-1402.
(d)Liu,H.;Gao,J.;Keel,E.T.Size-Expanded Analogues of dG and dC:Synthesis and Pairing Properties in DNA[J].J.Org.Chem.2005,70,639-647.
[34]Deakyne,C.A.;Meot-Ner(Mautner),M.Unconventional ionic hydrogen bonds.2.NH~+…π Complexes of onium ions with olefins and benzene derivatives[J].J.Am.Chem.Soc.1985,107,474-479.
[35]Guo,B.C.;Pumell,J.W.;Casfleman Jr.,A.W.The clustering reactions of benzene with sodium and lead ions[J].Chem.Phys.Lett.1990,168,155-160.
[36]de Vos,A.M.;Ultshc,M.;Kossiakoff,A.A.Human growth hormone and extracellular domain of its receptor:crystal structure of the complex[J].Science 1992,255,306-312.
(1)Lee,A.G.Curr.Opin.Struct.Biol.2002,12,547.
(2)Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Nature 2000,405,647.
(3)Lee,A.G.;East,J.M.Biochem.J.2001,356,665.
(4)(a)Inesi,G.J.Biol.Chem.1987,262,16338;
(b)de Meis,L.The Sarcoplasmic Reticulum,Wiley,New York 1981.
(5)Sun,W.;Kinsel,G.R.;Marynick,D.S.J.Phys.Chem.A.1999,103,4113.
(6)Moussatova,A.;Vazquez,M.-V.;Martinez,A;Dolgounitcheva,O.;Zakrzewski,V.G.;Ortiz,J.V.;Pedersen,D.B.;Simard,B.J.Phys.Chem.A.2003,107,9415.
(7)Jensen,F.J.Am.Chem.Soc.1992,114,9533.
(8)Russo,N.;Toscano,M.;Grand,A.J.Am.Chem.Soc.2001,123,10272
(9)Russo,N.;Toscano,M.;Grand,A.J.Phys.Chem.A.2003,107,11533
(10)Hoyau,S.;Ohanessian,G.J.Am.Chem.Soc.1997,119,2016.
(11)Bertran,J.;Rodriguez-Santiago,L.;Sodupe,M.J.Phys.Chem.B.1999,103,2310.
(12)Marino,T.;Russo,N.;Toscano,M.J.Inorg.Biochem.2000,79,179.
(13)Remko,M.;Rode,B.M.Chem.Phys.Lett.2000,316,489.
(14)Moision,R.M.;Armentrout,P.B.J.Phys.Chem.A.2002,106,10350.
(15)Ai,H.;Bu,Y;Li,P.Int.J Quantum.Chem.2003,94,205.
(16)Corral,I.;Mo,O.;Yanez,M.;Scott,A.P.;Radom,L.J.Phys.Chem.A.2003,107,10456.
(17)Dunbar,R.C.J.Phys.Chem.A.2000,104,8067.
(18)Tsipis,A.C.;Tsipis,C.A.;Valla,V.J.Mol.Struct.(Theochem).2003,630,81.
(19)(a)Bouchonet,S.;Hoppilliard,Y.Org.Mass Spectrom.1992,27,71.
(b)Bouchonet,S.;Flament,J.P.;Hoppilliard,Y.Rapid Commun.Mass Spectrom.1993,7,470.
(20)Hoyau,S.;Ohanessian,G.Chem.Eur J.1998,4,1561.
(21)Wyttenbach,T.;Witt,M.;Bowers,M.T.Int.J.Mass Spectrom.2001,243,182.
(22)Pulkkinen,S.;Noguera,M.;Rodriguez-Santiago,L.;Sodupe,M.;Bertran,J.Chem.Eur.J.2000,6,4393.
(23)Strittmatter,E.F.;Lemoff,A.S.;Williams,E.R.J.Phys.Chem.A.2000,104,9793.
(24)Rulisek,L.;Havlas,Z.J.Am.Chem.Soc.2000,122,10428.
(25)(a)Becke,A.D.J.Chem.Phys.1993,98,5648.
(b)Lee,C.;Yang,W.;Parr,R.G.Phys.ReV.B 1988,37,785.
(c)Stevens,P.J.;Devlin,F.J.;Chablowski,C.F.;Frisch,M.J.J.Phys.Chem.1994,98.11623.
(26)Dudev,T.;Lim,C.J.Phys.Chem.B.2004,108,4546.
(27)Ban,F.;Kusalik,P.;Weaver,D.F.J.Am.Chem.Soc.2004,126,4711.
(28)CRC Handbook of Chemistry and Physics,82nd Edition(2001-2002).
(29)Frisch,M.J.;Del Bene,J.E.;Binkley,J.S.;Schaefer,H.F.,Ⅲ.J.Chem.Phys.1986,84,2279.
(30)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.;Dapprieh,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.;Maliek,D.K.;Rabuck,A.D.;Raghavaehari,K.;Foresrnan,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.;Challaeombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Andres,J.L.;Gonzalez,C.;Head-Gordon,M.;Replogle,E.S.;Pople,J.A.Gaussian 98,Revision A.9;Gaussian,Inc.;Pittsburgh PA,1998.
(1)Glynn,I.M.J.Physiol.1993,462,1.
(2)Drake,S.K.;Lee,K.L.;Falke,J.J.Biochem.1996,35,6697.
(3)Yau,W.M.;Wimley,W.C.;Gawrisch,K.;White,S.H.Biochem.1998,37,14713.
(4)Lee,A.G.;East,J.M.Biochem.d.2001,356,665.
(5)Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Nature 2000,405,647.
(6)Frontera,A.;Quifionero,D.;Garau,C.;Costa,A.;Ballester,P.;Deya,P.M.J.Phys.Chem.A 2006,110,9307.
(7)(a)Felder,C.;Jiang,H.;Zhu,W.;Chen,K.;Silman,I.;Botti,S.A.;Sussman,J.L.J.Phys.Chem.A 2001,105,1326.
(b)Liu,T.;Zhu,W.;Gu,J.;Shen,J.;Luo,X.;Chen,G.;Puah,C.M.;Silman,I.;Chen,K.;Sussman,J.L.;Jiang,H.J.Phys.Chem.A 2004,108,9400.
(c)Tan.X.;Zhu,W.;Cui,M.;Luo,X.;Gu,J.;Silman,I.;Sussman,J.L.;Jiang,H.;Ji,R..;Chen,K.Chem.Phys.Lett.2001,349,113.
(8)(a)Dudev,T.;Lim,C.Acc.Chem.Res.2007,40,85.
(b)Dudev,T.;Lim,C.J.Am.Chem.Soc.2006,128,10541.
(9)Jensen,F.J.Am.Chem.Soc.1992,114,9533.
(10)(a)Hoyau,S.;Ohanessian,G.Chem.Eur.J.1998,4,1561.
(b)Hoyau,S.;Ohanessian,G.J.Am.Chem.Soc.1997,119,2016.
(11)Wyttenbach,T.;Witt,M.;Bowers,M.T.Int.J.Mass Spectrom.2001,243,182.
(12)Pulkkinen,S.;Noguera,M.;Rodri'guez-Santiago,L.;Sodupe,M.;Bertran,J.Chem.Eur.J.2000,6,4393.
(13)Bertran,J.;Rodriguez-Santiago,L.;Sodupe,M.J.Phys.Chem.B 1999,103,2310.
(14)Ma,J.C.;Dougherty,D.Chem.Rev.1997,97,1303.
(15)Ryahov,V.;Dunbar,R.C.J.Am.Chem.Soc.1999,121,2259.
(16)Jernigan,R.;Raghunathan,G.;Bahar,I.Curr.Opin.Struct.Biol.1994,4,256.
(17)Gouaux,E.;MacKinnon,R.Science 2005,310,1461.
(18)Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.R.;Montgomery,J.A.,Jr.;Vreven,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucci,B.;Cossi,M.; Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Bakken,V.;Adamo,C.;Jaramillo,J.;G-omperts,R.;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;Pomelli,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malick,D.K.;Rabuck,A.D.;Raghavachari,K.;Foresman,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Gonzalez,C.;Pople,J.A.Gaussian 03,revision B.05;Gaussian,Inc.:Wallingford,CT,2004.
(19)(a)Becke,A.D.J.Chem.Phys.1993,98,5648.
(b)Becke,A.D.Phys.Rev.1988,A38,3098.
(20)Lee,C.;Yang,W.;Parr,R.G.Phys.Rev.1988,B37,785.
(21)Becke,A.D.J.Chem.Phys.1993,98,1372.The BHandHLYP keyword in Gaussian employs a functional according to the formula,BHandHLYP:0.5×E_x(HF)+0.5×E_x(LSDA)+0.5×ΔE_x(Becke88)+E_c(LYP),which is not precisely the formulation proposed by A.D.Becke in his paper.
(22)Frisch,M.J.;Del Bene,J.E.;Binkley,J.S.;Schaefer,H.F.,Ⅲ.J.Chem.Phys.1986,84,2279.
(23)(a)Glendening,E.D.;Reed,A.E.;Carpenter,J.E.;Weinhold,F.NBO Version 3.1,
(b)Reed,A.E.;Curtiss,L.A.;Weinhold,F.Chem.Rev.1988,88,899.
(24)Breneman,C.M.;Wiberg,K.B.J.Comp.Chem.1990,11,361.
(25)CRC Handbook of Chemistry and Physws,82nd ed.;Lide,D.R.,Ed.;CRC Press:Cleveland,2001-2002.
(26)Marcus,Y.Chem.Rev.1988,88,1475.
(27)Alabugin,I.V.;Manoharan,M.;Peabody,S.;Weinhold,F.J.Am.Chem.Soc.2003,125,5973.
(28)de Vos,A.M.;Ultshc,M.;Kossiakoff,A.A.Science 1992,255,306.
(29)Pflugrath,J.W.;Wigand,G.;Huber,R.;Vertesy,L.J.Mol.Biol.1986,189,383.
(30)Rardin,R.L.;Tolmann,W.B.;Lippard,S.J.New J.Chem.1991,15,417.
(31)Rodriguez-Cruz,S.E.;Jockusch,R.A.;Williams,E.R.J.Am.Chem.Soc.1999,121,1986.
(32)Bezanilla,F.;Armstrong,C.M.d.Gen.Physiol.1972,60,588.
(33)Katz,A.K.;Glusker,J.P.;Beebe,S.A.;Bock,C.W.J.Am.Chem.Soc.1996,118,5752.
(34)(a)Falke,J.J.;Drake,S.K.;Hazard,A.L.;Peersen,O.B.Q.Rev.Biophys.1994,27,219.
(b)Drake,S.K.;Zimmer,M.A.;Kundrot,C.;Falke,J.J.J.Gen.Physiol.1997,110,173.
(c)Drake,S.K.;Zimmer,M.A.;Miller,C.L.;Falke,J.J.Biochemistry 1997,36,9917.
(35)Nonner,W.;Catacuzzeno,L.;Eisenberg,B.Biophys.J.2000,79,1976.
(36)Boda,D.;Busath,D.;Henderson,D.Sokolowsld,S.J.Phys.Chem.B 2000,104,8903.
(37)(a)Cony,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.Biochim.Biophys.Acta 2000,1509,1.
(b)Corry,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.Biophys.J.2001,80,195.
(c)Corry,B.;Vora,T.;Chung,S.H.Biochim.Biophys.Acta 2005,1711,72.
(d)Cony,B.;Chung,S.H.Cell.Mol.Life Sci.2006,63,301.
(38)Dudev,M.;Wang,J.;Dudev,T.;Lim,C.J.Phys.Chem.B 2006,110,1889.
(39)Dobler,M.Ionophores and Their Structures;Wiley:New York,1981.
[2]刘宣良:林进中:陈锦文.二零零三年诺贝尔化学奖[J].科学发展.2004,376,59-63.
[3](a)Toyoshima,C.;Nomura,H.Structural changes in the calcium pump accompanying the dissociation of calcium[J].Nature 2002,418,605-611.
(b)Toyoshima,C.;Nomura,H.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution[J].Nature 2000,405,647-655.
(c)Toyoshima,C.;Mizutani,T.Crystal structure of the calcium pump with a bound ATP analogue[J].Nature 2004,430,529-536.
(d)Toyoshima,C.;Nomura,H.;Tsuda,T Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues[J].Nature 2004,432,361-368.
(e)Obara,K.;Miyashita,N.;Xu,C.;Toyoshima,I.;Sugita,Y.;Inesi,G.;Toyoshima,C.Structural role of countertransport revealed in Ca~(2+)pump crystal structure in the absence of Ca~(2+)[J].Prec.Natl.Acad.Sci.USA 2005,102,14489-14496.
(f)Takahashi,M.;Kondou,Y;Toyoshima,C.Interdomain communication in calcium pump as revealed in the crystal structures with transmembrane inhibitors [J].Prec.Natl.Acad.Sci.USA 2007,104,5800-5805.
[4]Sorensen,T.L.;Moiler,J.V.;Nissen,P.Phosphoryl Transfer and Calcium Ion Occlusion in the Calcium Pump[J].Science 2004,304,1672-1675.
[5](a)Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
(b)Lee,A.G.A calcium pump made visible[J].Curr.Opin.Struct.Biol.2002,12,547-554.
[6]Xu,C.;Rice,W.J.;He,W.;Stokes,D.L.A structural modal for the catalytic cycle of Ca~(2+)-ATPase[J].J.Mol.Biol.2002,316,201-211.
[7]Ostwald,W.Elektrische Eigenschaften halbdurchlassiger Scheidewande[J].Z.Phys.Chem.1890,6,71-82.
[8]Michaelis,L.Contribution to the theory of permeability of membranes for electrolytes[J].J.Gen.Physiol.1925,8,33-59.
[9]Hodgkin,A.L.The ionic basis of nerve conduction.In Nobel Lectures in Physiology or Medicine 1963-1970,Amsterdam,Elsevier Publishing Company.1970.
[10]Huxley,A.F.The quanataive analysis of excitation and conduction in nerve.In Nobel Lectures in Physiology or Medicine 1963-1970,Amsterdam,Elsevier Publishing Company.1970.
[11]Doyle,D.;Cabral,J.;Pfuetzner,R.;Kuo,A.;Gulbis,J.;Cohen,S.;Chait,B.;MacKinnon,R.The structure of the potassium channel:Molecular basis of K~+conduction and sensitivity[J].Science 1998,280,69-77.
[12]Jiang,Y.;Lee,A.;Chen,J.;Cadene,M.;Chait,B.T.;MacKinnon,R.Crystal structure and mechanism of a calcium-gated potassium channel[J].Nature 2002a,417,515-522.
[13](a)Buoninsegni,F.T.;Bartolommei,G.;Moncelli,M.;Inesi,G.;Guidelli,R.Time-Resolved Charge Translocation by Sarcoplasmic Reticulum Ca~(2+)-ATPase Measured on a Solid Supported Membrane[J].Biophys.J.2004,86,3671-3686.
(b)Salvador,J.M.;Inesi,G.;Rigaud,J.-L.,Mata,A.M.Ca~(2+)Transport by Reconstituted Synaptosomal ATPase Is Associated with H~+ Countertransport and Net Charge Displacement[J].J.Biol.Chem.1998,273,18230-18234.
(c)Yu,X.;Carroll,S.;Rigaud,J.-L.;Inesi,G H~+ countertransport and electrogenicity of the sarcoplasmic reticulum Ca~(2+)pump in reconstituted proteoliposomes.[J].Biophys.J.1993,64,1232-1242.
(d)Zhang,Z.;Lewis,D.;Strock,C.;Inesi,G.Detailed Characterization of the Cooperative Mechanism of Ca~(2+)Binding and Catalytic Activation in the Ca~(2+)Transport(SERCA)ATPase[J].Biochemistry 2000,39,8758-8767.
[14](a)Drake,S.K.;Lee,K.L.;Falke,J.J.Tuning the equilibrium ion affinity and selectivity of the EF-hand calcium binding motif:Substitutions at the gateway positions[J].Biochemistry 1996,35,6697-6075.
(b)Falke,J.J.;Drake,S.K.;Hazard,A.L.;Peersen,O.B.Molecular tuning of ion binding to calcium signaling proteins[J].Q.Rev.Biophys.1994,27,219-290.
(c)Drake,S.K.; Zimmer,M.A.;Kundrot,C.;Falke,J.J.Molecular Tuning of an EF-Hand-like Calcium Binding Loop.Contributions of the Coordinating Side Chain at Loop Position 3[J].J.Gen.Physiol.1997,110,173-184.
(d)Drake,S.K.;Zirnmer,M.A.;Miller,C.L.;Falke,J.J.Optimizing the metal binding parameters of an EF-hand-like calcium chelation loop:Coordinating side chains play a more important tuning role than chelation loop flexibility[J].Biochemislry 1997,36,9917-9926.
[15]Sugita,Y.;Miyashita,N.;Ikeguchi,M.;Kidera,A.;Toyoshima,C.Protonation of the Acidic Residues in the Transmembrane Cation-Binding Sites of the Ca~(2+)Pump[J].J.Am.Chem.Soc.2005,127,6150-6151.
[16]Costa,V.;Carloni,P.Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca~(2+)-ATPase:Insights from molecular modeling[J].Proteins:Struct.,Funct.,Genet..2003,50,104-113.
[17]Dudev,T.;Lim,C.Effect of carboxylate-bindmg mode on metal binding and electivity in proteins[J].Acc.Chem.Res.2007,40,85-93.
[18]朱维良;蒋华良;陈凯先;嵇汝运;曹阳.分子间相互作用的量子化学研究方法[J].化学进展 1999,11,247-253.
[1]Lee,A.G.A calcium pump made visible[J].Curr.Opin.Struct.Biol.2002,12,547-554.
[2]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reficulun at 2.6A resolution[J].Nature 2000,405,647-655.
[3]Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
[4](a)Inesi,G.Sequential mechanism of calcium binding and translocation in sarcoplasmic reticulum adenosine triphosphatase[J].J.Biol.Chem.1987,262,16338-16342;
(b)de Meis,L.The Sarcoplasmic Reticulum:Transport and Energy Transduction,Wiley,New York 1981,2,1-163.
[5]Sun,W.;Kinsel,G.R.;Matynick,D.S.Computational Estimates of the Gas-Phase Basicity and Proton Affinity of Glutamic Acid[J].J.Phys.Chem.A 1999,103,4113-4117.
[6]Moussatova,A.;Vazquez,M.-V.;Martinez,A.;Dolgounitcheva,O.;Zakrzewski,V.G.;Ortiz,J.V.;Pedersen,D.B.;Simard,B.Theoretical Study of the Structure and Bonding of a Metal-DNA Base Complex:Al-Guanine[J].J.Phys.Chem.A 2003,107,9415-9421.
[7]Jensen,F.Structure and stability of complexes of glycine and glycine methyl analogs with H~+,Li~+,and Na~+[J].J.Am.Chem.Soc.1992,114,9533-9537.
[8]Russo,N.;Toscano,M.;Grand,A.Bond Energies and Attachments Sites of Sodium and Potassium Cations to DNA and RNA Nucleic Acid[J].J.Am.Chem.Soc.2001,123,10272-10279.
[9]Russo,N.;Toscano,M.;Grand,A.Gas-Phase Absolute Ca~(2+)and Mg~(2+)Affinity for Nucleic Acid Bases.A Theoretical Determination[J].J.Phys.Chem.A 2003,107,11533-11538.
[10]Hoyau,S.;Ohanessian,G.Absolute Affinities of α-Amino Acids for Cu~+ in the Gas Phase.ATheoretical Study[J].J.Am.Chem.Soc.1997,119,2016-2024.
[11]Bertran,J.,Rodriguez-Santiago,L.;Sodupe,M.The Different Nature of Bonding in Cu~+-Glycme and Cu~(2+)-Glyclne[J].J.Phys.Chem.B 1999,103,2310-2317.
[12]Marine,T.;Russo,N.,Toscano,M.Gas-phase metal ion(Li~+,Na~+,Cu~+)affinities of glycine and alanine[J].J Inorg.Biochem.2000,79.179-185.
[13]Remko,M.;Rode,B.M.Bivalent cation binding effect on formation of the peptide bond[J].Chem.Phys.Lett.2000,316,489-494.
[14]Moision,R.M.,Armentrout,P.B.Experimental and Theoretical Dissection of Sodium Cation/Glycine Interactions[J].J Phys.Chem.A 2002,106,10350-10362.
[15]Ai,H.;Bu,Y.;Li,P.Intramolecular proton transfer induced by divalent alkali earth metal cation in the gas state[J].Int.J Quantum.Chem.2003,94,205-214.
[16]Corral,I.;Me,O.;Yanez,M.;Scott,A.P.;Radom,L.Interactions between Neutral Molecules and Ca~(2+):An Assessment of Theoretical Procedures[J].J Phys.Chem.A 2003,107,10456-10461.
[17]Dunbar,R.C.Complexation of Na~+ and K~+ to Aromatic Amino Acids:A Density Functional Computational Study of Cation-π Interactions[J].J Phys.Chem.A 2000,104,8067-8074.
[18]Tsipis,A.C.;Tsipis,C.A.;Valla,V.Quantum chemical study of the coordination of glycolic acid conformers and their conjugate bases to[Ca(OH_2)_n]~(2+)(n=0-4)ions[J].J Mol.Struct.(Theochem.)2003,630,81-100.
[19](a)Bouchonet,S.;Hoppilliard,Y.Proton and sodium ion affinities of glvcine and its sodium salt in the gas phase.Ab initio calculations[J].Org.Mass Spectrom.1992,27,71-76.
(b)Bouchonet,S.;Flament,J.P.;Hoppilliard,Y.Desorption-ionization and in-flight fragmentation of monoalkali-glycine adducts:Plasma-desorption mass spectrometry and Ab initio calculations[J].Rapid Commun.Mass Spectrom.1993,7,470-476.
[20]Hoyau,S.;Ohanessian,G Interaction of Alkali Metal Cations(Li~+-Cs~+)with Glycine in the Gas Phase:A Theoretical Study[J].Chem.Eur.J.1998,4,1561-1569.
[21]Wyttenbach,T.;Witt,M.;Bowers,M.T.On the Stability of Amino Acid Zwitterions in the Gas Phase:The Influence of Derivatization,Proton Affinity,and Alkali Ion Addition[J].J.Am.Chem.Soc.2000,122,3458-3464.
[22]Pulkkinen,S.;Noguera,M.;Rodriguez-Santiago,L.;Sodupe,M.;Bertran,J.Gas Phase Intramolecular Proton Transfer in Cationized Glycine and Chlorine Substituted Derivatives(M-Gly,M=Na~+,Mg~(2+),Cu~+,Ni~+,and Cu~(2+)):Existence of Zwitterionic Structures?[J].Chem.Eur.J.2000,6,4393-4399.
[23]Strittmatter,E.F.;Lemoff,A.S.;Williams,E.R.Structure of Cationized Glycine,Gly·M~(2+)(M=Be,Mg,Ca,Sr,Ba),in the Gas Phase:Intrinsic Effect of Cation Size on Zwitterion Stability[J].J.Phys.Chem.A 2000,104,9793-9796.
[24]Rulisek,L.;Havlas,Z.Theoretical Studies of Metal Ion Selectivity.1.DFT Calculations of Interaction Energies of Amino Acid Side Chains with Selected Transition Metal Ions(Co~(2+),Ni~(2+),Cu~(2+),Zn~(2+),Cd~(2+),and Hg~(2+))[J].J.Am.Chem.Soc.2000,122,10428-10439.
[25](a)Becke,A.D.Density-functional thermochemistry.Ⅲ.The role of exact exchange[J].J.Chem.Phys.1993,98,5648-5652.
(b)Lee,C.;Yang,W.;Parr,R.G.Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density[J].Phys.ReV.B 1988,37,785-789.
(c)Stevens,P.J.;Devlin,F.J.;Chablowski,C.F.;Frisch,M.J.Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force[J].J.Phys.Chem.1994,98,11623-11627.
[26]Dudev,T.;Lim,C.Monodentate versus Bidentate Carboxylate Binding in Magnesium and Calcium Proteins:What Are the Basic Principles?[J].J.Phys.Chem.B 2004,108,4546-4557.
[27]Ban,F.;Kusalik,P.;Weaver,D.F.Density Functional Theory Investigations on the Chemical Basis of the Selectivity Filter in the K~+ Channel Protein[J].J.Am.Chem.Soc.2004,126,4711-4716.
[28]Frisch,M.J.;Del Bene,J.E.;Binkley,J.S.;Schaefer,H.F.,Ⅲ.Extensive theoretical studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[29]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press: Cleveland,82nd edn,2001-2002.
[30]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.;Chen,W.;Wong,M.W.,Andres,J.L.;Gonzalez,C.;Head-Gordon,M.;Replogle,E.S.;Pople,J.A.Gaussian 98,Revision A.9;Gaussian,Inc.;Pittsburgh PA,1998.
[1]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6A resolution[J].Nature 2000,405,647-655.
[2](a)Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683;
(b)Lee,A.G.A calcium pump made visible[J].Curr.Opin.Struct.Biol.2002,12,547-554.
[3]Xu,C.;Rice,W.J.;He,W.;Stokes,D.L.A structural modal for the catalytic cycle of Ca~(2+)-ATPase[J].J Mol.Biol.2002,316,201-211.
[4]Sorensen,T.L.;Moiler,J.V.;Nissen,P.Phosphoryl Transfer and Calcium Ion Occlusion in the Calcium Pump[J].Science 2004,304,1672-1675.
[5]Costa,V.;Carloni,P.Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca~(2+)-ATPase:Insights from molecular modeling[J].Proteins:Struct.,Funct.,Genet..2003,50,104-113.
[6](a)Dudev,T;Lim,C.Monodentate versus Bidentate Carboxylate Binding in Magnesium and Calcium Proteins:What Are the Basic Principles?[J].J.Phys.Chem.B 2004,108,4546-4557;
(b)Babu,C.S.;Dudev,T.;Casareno,R.;Cowan,J.A.;Lim,C.A Combined Experimental and Theoretical Study of Divalent Metal Ion Selectivity and Function in Proteins:Application to E.coli Ribonuclease H1[J].J.Am.Chem.Soc.2003,125,9318-9328;
(c)Dudev,T.;Lin,Y.L.;Dudev,M.;Lira,C.First-Second Shell Interactions in Metal Binding Sites in Proteins:A PDB Survey and DFT/CDM Calculations[J].J.Am.Chem.Soc.2003,125,3168-3180;
(d)Dudev,T.;Lim,C.Principles Governing Mg,Ca,and Zn Binding and Selectivity in Proteins[J].Chem.Rev.2003,103,773-788;
(e)Dudev,T.;Lim,C.A DFT/CDM Study of Metal-Carboxylate Interactions in Metalloproteins:Factors Governing the Maximum Number of Metal-Bound Carboxylates[J].J Am.Chem.Soc.2006,128,1553-1561.
[7]Xiang,F.;Bu,Y.;Ai,H.;Li,P.The Coupling Character of Ca~(2+)with Glutamic Acid:Implication for the Conformational Behavior and Transformation of Ca~(2+)-ATPase in Transmembrane Ca~(2+)Channel[J].J.Phys.Chem.B 2004,108,17628-17638.
[8]Jockusch,R.A.;Lemoff,A.S.;Williams,E.R.Hydration of Valine-Cation Complexes in the Gas Phase:On the Number of Water Molecules Necessary to Form a Zwitterion[J].J.Phys.Chem.A 2001,105,10929-10942.
[9]Carrell,C.J.;Carrell,H.L.;Erlebacher,J.;Glusker,J.P.Structural aspects of metal ion carboxylate interactions[J].J.Am.Chem.Soc.1988,110,8651-8656.
[10]Tiraboschi,G.;Roques,B.;Gresh,N.Joint quantum chemical and polarizable molecular mechanics investigation of formate complexes with penta- and hexahydrated Zn~(2+):Comparison between energeties of model bidentate,monodentate,and through-water Zn~(2+)binding modes and evaluation of nonadditivity effects[J].J.Comput.Chem.1999,20,1379-1390.
[11]Abola,E.E.;Sussman,J.L.;Prilusky,J.;Manning,N.O.Protein Data Bank archives of three-dimensional macromolecular structures.[J].Methods Enzymol.1997,277,556-571.
[12]Yang,W.;Jones,L.M.;Isley,L.;Ye,Y.;Lee,H.-W.;Wilkins,A.;Liu,Z.;Hellinga,H.W.;Malchow,R.;Ghazi,M.;Yang,J.J.Rational Design of a Calcium-Binding Protein[J].J.Am.Chem.Soc.2003,125,6165-6171.
[13]Pidcock,E.;Moore,G.R.Structural characteristics of protein binding sites for calcium and lanthanide ions[J].J.Biol.Inorg.Chem.2001,6,479-489.
[14]Sugita,Y.;Miyashita,N.;Ikeguchi,M.;Kidera,A.;Toyoshima,C.Protonation of the Acidic Residues in the Transmembrane Cation-Binding Sites of the Ca~(2+)Pump [J].J.Am.Chem.Soc.2005,127,6150-6151.
[15]Bernal-Uruchurtu,M.I.;Ortega-Blake,I.A refined Monte Carlo study of Mg~(2+)and Ca~(2+)hydration[J].J.Chem.Phys.1995,103,1588-1598.
[16](a)Becke,A.D.Density-functional thermochemistry.Ⅲ.The role of exact exchange[J].J.Chem.Phys.1993,98,5648-5652;
(b)Lee,C.;Yang,W.;Parr,R.G.Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density[J].Phys.Rev.B 1988,37,785-789;
(c)Stevens,P.J.;Devlin,F.J.;Chablowski,C.F.;Frisch,M.J.Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields[J].J.Phys.Chem.1994,98,11623-11627.
[17]Peschke,M.;Blades,A.T.;Kebarle,P.Binding Energies for Doubly-Charged Ions M~(2+)=Mg~(2+),Ca~(2+)and Zn~(2+)with the Ligands L=H_2O,Acetone and N-methylacetamide m Complexes ML_n~(2+)for n=1 to 7 from Gas Phase Equilibria Determinations and Theoretical Calculations[J].J.Am.Chem.Soc.2000,122,10440-10449.
[18]Tsipis,A.C.;Tsipis,C.A.;Valla,V.Quantum chemical study of the coordination of glycolic acid conformers and their conjugate bases to [Ca(OH_2)_n]~(2+)(n=0-4)ions[J].J.Mol.Struct.(THEOCHEM)2003,630,81-100.
[19]Ai,H.;Bu,Y.Reservation Energy Bonds and Structural Stability of Series of Multihydrated(nine=1-10)Glycine-H~+M~+(M=Li,Na,or K)Complexes[J].J.Phys.Chem.B 2004,108,1241-1254.
[20]Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.K;Montgomery,J.A.;Vreven,Jr,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucci,B.;Cossi,M.;Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Adamo,C.;Jaramillo,J.;Gomperts,R.;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;PomeUi,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malick,D.K.;Rabuck,A.D.;Raghavachari,K.;Foresrnan,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Wong,W.Chen,;M.W.;Gonzalez,C.;Pople,J.A.GAUSSIAN 03(Revision B.05);Gaussian,Inc.,Pittsburgh,PA,2003.
[21]Frisch,M.J.;Bene,J.E.D.;Binkley,J.S.;Schaefer Ⅲ,H.F.Extensive theoretical studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[22]Cances,E.;Mennucci,B.;Tomasi,J.A new integral equation formalism for the polarizable continuum model:Theoretical background and applications to isotropic and anisotropie dielectrics[J].J.Chem.Phys.1997,107,3032-3041.
[23]Cossi,M.;Barone,V.;Mennucci,B.;Tomasi,J.Ab initio study of ionic solutions by a polarizable continuum dielectric model[J].Chem.Phys.Lett.1998,286,253-260.
[24]Mennucci,B.;Tomasi,J.Continuum solvation models:A new approach to the problem of solute's charge distribution and cavity boundaries[J].J.Chem.Phys.1997,106,5151-5158.
[25]Cossi,M.;Scalmani,G.;Rega,N.;Barone,V.New developments in the polarizable continuum model for quantum mechanical and classical calculations on molecules in solution[J].J.Chem.Phys.2002,117,43-54.
[26]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press:Cleveland,82nd edn,2001-2002.
[27]Corral,I.;Me,O.;Yanez,M.;Scott,A.P.;Radom,L.Interactions between Neutral Molecules and Ca~(2+):An Assessment of Theoretical Procedures[J].J.Phys.Chem.A 2003,107,10456-10461.
[1]Glynn,I.M.Annual review prize lecture.'All hands to the sodium pump'[J].J.Physiol.1993,462,1-30.
[2]Drake,S.K.;Lee,K.L.;Falke,J.J.Tuning the equilibrium ion affinity and selectivity of the EF-hand calcium binding motif:Substitutions at the gateway positions[J].Biochemistry 1996,35,6697-6075.
[3]Yau,W.M.;Wimley,W.C.;Gawrisch,K.;White,S.H.The Preference of Tryptophan for Membrane Interfaces[J].Biochemistry.1998,37,14713-14718.
[4]Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
[5]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticul[J].Nature 2000,405,647-655.
[6]Frontera,A.;Quinonero,D.;Garau,C.;Costa,A.;Ballester,P.;Deya,P.M.MP2 Study of Cation-(π)_n-π Interactions(n=1-4)[J].J.Phys.Chem.A 2006,110,9307-9309.
[7](a)Felder,C.;Jiang,H.;Zhu,W.;Chen,K.;Silman,I.;Botti,S.A.;Sussman,J.L.Quantum/Classical Mechanical Comparison of Cation-π Interactions between Tetramethylammonium and Benzene[J].J.Phys.Chem.A 2001,105,1326-1333.
(b)Liu,T.;Zhu,W.;Gu,J.;Shen,J.;Luo,X.;Chen,G.;Puah,C.M.;Silman,I.;Chen,K.;Sussman,J.L.;Jiang,H.Additivity of Cation-π Interactions:An ab Initio Computational Study on π-Cation-π Sandwich Complexes[J].J.Phys.Chem.A 2004,108,9400-9405.
(c)Tan.X.;Zhu,W.;Cui,M.;Luo,X.;Gu,J.;Silman,I.;Sussman,J.L.;Jiang,H.;Ji,R.;Chen,K.Spine high-throughput crystallization,crystal imaging and recognition techniques:current state,performance analysis,new technologies and future aspects[J].Chem.Phys.Lett.2001,349,113-1149.
[8](a)Dudev,T.;Lim,C.Effect of carboxylate-binding mode on metal binding and electivity in proteins[J].Acc.Chem.Res.2007,40,85-93.
(b)Dudev,T.;Lim,C.Competition between Protein Ligands and Cytoplasmic Inorganic Anions for the Metal Cation:A DFT/CDM Study[J].J.Am.Chem.Soc.2006,128,10541-10548.
[9]Jensen,F.Structure and stability of complexes of glycine and glycine methyl analogs with H~+,Li~+,and Na~+[J].J.Am.Chem.Soc.1992,114,9533-9537.
[10](a)Hoyau,S.;Ohanessian,G.Interaction of alkali metal cations(Li~+-Cs~+)with glycine in the gas phase:A theoretical study[J].Chem.Eur.J.1998,4,1561-1569.
(b)Hoyau,S.;Ohanessian,G.Absolute Affinities of α-Amino Acids for Cu~+ in the Gas Phase.A Theoretical Study[J].J.Am.Chem.Soc.1997,119,2016-2024.
[11]Wyttenbach,T.;Witt,M.;Bowers,M.T.On the question of salt bridges of cationized amino acids in the gas phase:glycine and arginine[J].Int.J.Mass Spectrom.2001,243,182-183.
[12]Pulkkinen,S.;Noguera,M.;Rodn'guez-Santiago,L.;Sodupe,M.;Bertran,J.Gas Phase Intramolecular Proton Transfer in Cationized Glycine and Chlorine Substituted Derivatives(M-Gly,M=Na~+,Mg~(2+),Cu~+,Ni~+,and Cu~(2+)):Existence of Zwitterionic Structures?[J].Chem.Eur.J.2000,6,4393-4399.
[13]Bertran,J.;Rodriguez-Santiago,L.;Sodupe,M.The Different Nature of Bonding in Cu~+-Glycine and Cu~(2+)-Glycine[J].J.Phys.Chem.B 1999,103,2310-2317.
[14]Ma,J.C.;Dougherty,D.The Cation-π Interaction[J].Chem.Rev.1997,97,1303-1324.
[15]Ryahov,V.;Dunbar,R.C.Interactions of Phenol and Indole with Metal Ions in the Gas Phase:Models For Tyr and Trp Side-Chain Binding[J].J.Am.Chem.Soc.1999,121,2259-2268.
[16]Jemigan,R.;Raghunathan,G.;Bahar,I.Characterization of.interactions and metal ion binding sites in proteins[J].Curr.Opin.Struct.Biol.1994,4,256-263.
[17]Gouaux,E.;MacKinnon,R.Principles of selective ion transport in channels and pumps[J].Science 2005,310,1461-1465.
[18]Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.R.;Montgomery,J.A.,Jr.;Vreven,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucci,B.;Cossi,M.; Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Bakken,V.;Adamo,C.;Jaramillo,J.;Gomperts,R;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;Pomelli,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malice D.K.;Rabuck,A.D.;Raghavachari,K.;Foresman,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Gonzalez,C.;Pople,J.A.Gaussian 03,revision B.05;Gaussian,Inc.:Wallingford,CT,2004.
[19](a)Becke,A.D.Density-functional thermochemistry.Ⅲ.The role of exact exchange[J].J.Chem.Phys.1993,98,5648-5652.
(b)Becke,A.D.Density-functional exchange-energy approximation with correct asymptotic behavior[J].Phys.Rev.1988,A38,3098-3104.
[20]Lee,C.;Yang,W.;Parr,R G.Development of the colle-salvetti correlation energy formula into a functional of the electron density[J].Phys.Rev.1988,B37,5-789.
[21]Becke,A.D.A new mixing of Hartree-Fock and local density-functional theories [J].J.Chem.Phys.1993,98,1372-1377.The BHandHLYP keyword in Gaussian employs a functional according to the formula,BHandHLYP:0.5×E_x(HF)+0.5×E_x(LSDA)+0.5×ΔE_x(Becke88)+E_c(LYP),which is not precisely the formulation proposed by A.D.Becke in his paper.
[22]Frisch,M.J.;Del Bene,J.E.;Binldey,J.S.;Schaefer,H.F.,Ⅲ.Extensive theoretical-studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[23](a)Glendening,E.D.;Reed,A.E.;Carpenter,J.E.;Weinhold,F.NBO Version 3.1,
(b)Reed,A.E.;Curtiss,L.A.;Weinhold,F.Intermolecular interactions from a natural bond orbital,donor-acceptor viewpoint[J].Chem.Rev.1988,88,899-926.
[24]Breneman,C.M.;Wiberg,K.B.Determining atom-centered monopoles from molecular electrostatic potentials.The need for high sampling density in formamide conformational analysis[J].J.Comp.Chem.1990,11,361-373.
[25]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press:Cleveland,82nd edn,2001-2002.
[26]Marcus,Y.Ionic radii in aqueous solutions[J].Chem.Rev.1988,88,1475-1498.
[27]Alabugin,I.V.;Manoharan,M.;Peabody,S.;Weinhold,F.Electronic Basis of Improper Hydrogen Bonding:A Subtle Balance of Hyperconjugation and Rehybridization[J].J.Am.Chem.Soc.2003,125,5973-5987.
[28]de Vos,A.M.;Ultshc,M.;Kossiakoff,A.A.American Chemistry in Context:Chemistry and Modem Society[J].Science 1992,255,306-312.
[29]Pflugrath,J.W.;Wigand,G.;Huber,R.;Vertesy,L.Crystal structure determination,refinement and the molecular model of the α-amylase inhibitor Hoe-467A[J].J Mol.Biol.1986,189,383-386.
[30]Rardin,R.L.;Tolmann,W.B.;Lippard,S.J.Monodentate carboxylate complexes and the carboxylate shift:implications for poly-metalloprotein structure and function[J].New J.Chem.1991,15,417-430.
[31]Rodriguez-Cruz,S.E.;Jockusch,R.A.;Williams,E.R.Binding Energies of Hexahydrated Alkaline Earth Metal Ions,M~(2+)(H_2O)_6,M=Mg,Ca,Sr,Ba:Evidence of Isomeric Struetures for Magnesium[J].J.Am.Chem.Soc.1999,121,1986-1987.
[32]Bezanilla,F.;Armstrong,C.M.Negative Conductance Caused by Entry of Sodium and Cesium Ions into the Potassium Channels of Squid Axons[J].J.Gen.Physiol.1972,60,588-608.
[33]Katz,A.K.;Glusker,J.P.;Beebe,S.A.;Bock,C.W.Calcium Ion Coordination:A Comparison with That of Beryllium,Magnesium,and Zinc[J].J.Am.Chem.Soc.1996,118,5752-5763.
[34](a)Falke,J.J.;Drake,S.K.;Hazard,A.L.;Peersen,O.B.Molecular tuning of ion binding to calcium signaling proteins[J].Q.Rev.Biophys.1994,27,219-290.
(b)Drake,S.K.;Zimmer,M.A.;Kundrot,C.;Falke,J.J.Molecular Tuning of an EF-Hand-like Calcium Binding Loop.Contributions ofthe Coordinating Side Chain at Loop Position 3[J].J.Gen.Physiol.1997,110,173-184.
(c)Drake,S.K.;Zimmer,M A.;Miller,C.L.;Falke,J.J.Optimizing the metal binding parameters of an EF-hand-like calcium chelation loop:Coordinating side chains play a more important tuning role than chelation loop flexibility[J].Biochemistry 1997,36,9917-9926.
[35]Nonner,W.;Catacuzzeno,L.;Eisenberg,B.Binding and selectivity in L-type calcium channels:a mean spherical approximation[J].Biophys.J.2000,79,1976-1992.
[36]Boda,D.;Busath,D.;Henderson,D.Sokolowski,S.Monte Carlo Simulations of the Mechanism for Channel Selectivity:The Competition between Volume Exclusion and Charge Neutrality[J].J.Phys.Chem.B 2000,104,8903-8910.
[37](a)Corry,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.A model of calcium channels[J].Biochim.Biophys.Acta 2000,1509,1-6.
(b)Corry,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.Mechanisms of permeation and selectivity in calcium channels[J].Biophys.J.2001,80,195-214.
(c)Corry,B.;Vora,T.;Chung,S.H.Electrostatic basis of valence selectivity in cationic channels[J].Biochim.Biophys.Acta 2005,1711,72-86.
(d)Corry,B.;Chung,S.H.Mechanisms of valence selectivity in biological ion channels[J].Cell.Mol.Life Sci.2006,63,301-315.
[38]Dudev,M.;Wang,J.;Dudev,T;Lim,C.Factors Governing the Metal Coordination Number in Metal Complexes from Cambridge Structural Database Analyses[J].J.Phys.Chem.B 2006,110,1889-1895.
[39]Dobler,M.Ionophores and Their Structures;Wiley:New York,1981.
[1]Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Crystal structure of the calcium pump of sarcoplasmic reticul[J].Nature 2000,405,647-655.
[2]Kohtani,M.;Jarrold,F.;Wee,S.;O'Hair R.A.J.Metal Ion Interactions with Polyalanine Peptides[J].J.Phys.Chem.B 2004,108,6093-6097.
[3]Dudev,T.;Lim,C.Effect of carboxylate-binding mode on metal binding and electivity in proteins[J].Acc.Chem.Res.2007,40,85-93.
[4](a)Xiang,F.;Bu,Y.;Ai,H.;Li,P.The Coupling Character of Ca~(2+)with Glutamic Acid:Implication for the Conformational Behavior and Transformation of Ca~(2+)-ATPase in Transmembrane Ca~(2+)Channel[J].J.Phys.Chem.B 2004,108,17628-17638.
(b)Xiang,F.;Li,P.;Yan,S.;Sun,L.;Cukier,R.;Bu,Y.Hydration effect on interaction mode between glutamic acid and Ca~(2+)and its biochemical implication:a theoretical explorationw[J].New J.Chem.2006,30,890-900.
(c)Xiang,F.;Cukier,R.I.;Bu,Y.Ca~(2+)Selectivity of the Sarcoplasmic Reticulum Ca~(2+)-ATPase at the Enzyme-Water Interface and in the Ca~(2+)Entrance Channel [J].J.Phys.Chem.B 2007,111,12282-12293.
[5]Kim,K.S.;Tarakeshwar,P.;Lee,J.Y.Molecular Clusters of-Systems:Theoretical Studies of Structures,Spectra,and Origin of Interaction Energies[J].Chem.Rev.2000,100,4145-4185
[6]Crowley,P.B.;Golovin,A.Cation-π Interactions in Protein-Protein Interfaces[J].Proteins:Struct.,Funct.,Genet.,2005,59,231-239
[7]Lee,A.G.;East,J.M.What the structure of a calcium pump tells us about its mechanism[J].Biochem.J.2001,356,665-683.
[8]Costa,V.;Carloni,P.Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca~(2+)-ATPase:Insights from molecular modeling[J].Proteins:Struct..Funct.,Genet.,2003,50,104-113.
[9]Huang,Y.;Bu,Y.Cooperative Dynamics Mechanism of Calcium Ions Binding to Sarcoplasmic Reticulum Ca~(2+)-ATPase:Insights from Molecular Dynamics Simulations[J].J.Phys.Chem.B(to be published)
[10]Gouaux,E.;MacKinnon,R.Principles of Selective Ion Transport in Channels and Pumps[J].Science 2005,310,1461-1465.
[11]Reddy,A.S.;Vijay,D.;Sastry,G.M.;Sastry,G.N.From Subtle to Substantial:Role of Metal Ions on π-π Interactions[J].J.Phys.Chem.B 2006,110,2479-2481
[12]Heginbotham,L.;MacKinnon,R.The aromatic binding site for tetraethylammonium ion on potassium channels[J].Neuron 1992,8,483-491.
[13](a)Doyle,A.D.;Cabral,M.J.;Pfuetzner,A.R.;Kuo,A.;Gulbis,M.J.;Cohen,L.S.;Chait,T.B.;MacKinnon,R.The Structure of the Potassium Channel:Molecular Basis of K~+ Conduction and Selectivity[J].Science 1998,280,69-77.
(b)French,J.R.;Shoukimas,J.J.Blockage of squid axon potassium conductance by internal tetra-N-alkylammonium ions of various sizes[J].Biophys.J.1981,34,271-291.
[14]Ma,J.C.;Dougherty,D.A.The Cation-π Interaction[J].Chem.Rev.1997,97,1303-1324.
[15]Coletti,C.;Re,N.Theoretical Study of Alkali Cation-Benzene Complexes:Potential Energy Surfaces and Binding Energies with Improved Results for Rubidium and Cesium[J].J.Phys.Chem.A 2006,110,6563-6570.
[16]Cheng,J.;Zhu,W.;Tang,Y.;Xu,Y.;Li,Z.;Chen,K.;Jiang,H.Effect of cation-π interaction on NMR:A theoretical investigation on complexes of Li~+,Na~+,Be~(2+),and Mg~(2+)with aromatics[J].Chem.Phys.Lett.2006,422,455-460.
[17]Felder,C.;Jiang,H.;Zhu,W.;Chen,K.;Silman,I.;Botti,S.A.;Sussman,J.L.Quantum/Classical Mechanical Comparison of Cation-π Interactions between Tetramethylammonium and Benzene[J].J.Phys.Chem.A 2001,105,1326-1333.
[18]Reddy,A.S.;Sastry,G.N.Cation[M=H~+,Li~+,Na~+,K~+,Ca~(2+),Mg~(2+),NH_4~+,and NMe_4~+]Interactions with the Aromatic Motifs of Naturally Occurring Amino Acids:A Theoretical Study[J].J.Phys.Chem.A 2005,109,8893-8903.
[19]Frontera,A.;Quinonero,D.;Garau,C.;Costa,A;BaUester,P.;Deya,P.M.MP2Study of Cation-(π)_n-π Interactions(n=1-4)[J].J.Phys.Chem.A 2006,110, 9307-9309.
[20]Li,H.;Boatz,J.A.;Gordon,M.S.Cation-Cation π-π Stacking in Small Ionic Clusters of 1,2,4-Triazolium[J].J.Am.Chem.Soc.2008,130,392-393.
[21]Ryzhov,V.;Dunbar,R.C.Interactions of Phenol and Indole with Metal Ions in the Gas Phase:Models For Tyr and Trp Side-Chain Binding[J].J.Am.Chem.Soc.1999,121,2259-2268
[22]Frisch,M.J.;Trucks,G.W.;Sehlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.R.;Montgomery,J.A.,Jr.;Vreven,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucei,B.;Cossi,M.;Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Bakken,V.;Adamo,C.;Jaramillo,J.;Gomperts,R.;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;Pomelli,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malick,D.K.;Rabuck,A.D.;Raghavaehari,K.;Foresman,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Gonzalez,C.;Pople,J.A.Gaussian 03,revision B.05;Gaussian,Inc.:Wallingford,CT,2004.
[23]Head-Gordon M.,Pople J.A.,Frisch M.J.MP2 energy evaluation by direct methods[J].Chem.Phys.Lett.1988,153,503-509.
[24]Rappe,A.K.;Bernstein,E.R.Ab Initio Calculation of Nonbonded Interactions:Are We There Yet?[J].J.Phys.Chem.A 2000,104,6117-6128.
[25]Frisch,M.J.;Bene,J.E.D.;Binkley,J.S.;Schaefer Ⅲ,H.F.Extensive theoretical studies of the hydrogen-bonded complexes(H_2O)_2,(H_2O)_2H~+,(HF)_2,(HF)_2H~+,F_2H~-,and(NH_3)_2[J].J.Chem.Phys.1986,84,2279-2289.
[26](a)Glendening,E.D.;Reed,A.E.;Carpenter,J.E.;Weinhold,F.NBO Version 3.1,
(b)Reed,A.E.;Curtiss,L.A.;Weinhold,F.Intermolecular interactions from a natural bond orbital,donor-accepter viewpoint[J].Chem.Rev.1988,88,899-926.
[27]Breneman,C.M.;Wiberg,K.B.Determining atom-centered monopoles from molecular electrostatic potentials.The need for high sampling density in fotmamide conformational analysis[J].J.Comp.Chem.1990,11,361-373.
[28]Lide,D.R.CRC Handbook of Chemistry and Physics[M].CRC Press:Cleveland,82nd edn,2001-2002.
[29]Tan.X.;Zhu,W.;Cui,M.;Luo,X.;Gu,J.;Silman,I.;Sussman,J.L.;Jiang,H.;Ji,R..;Chen,K.Spine high-throughput crystallization,crystal imaging and recognition techniques:current state,performance analysis,new technologies and future aspects[J].Chem.Phys.Lett.2001,349,113-1149.
[30]Reed,A.E.;Curtiss,L.A.;Weinhold,E;Intermolecular Interactions from a Natural Bond Orbital,Donor-Accepter Viewpoint[J].Chem.Rev.1988,88,899-926.
[31]Carpenter,J.E.;Weinhold,F.J.Mol.Struct.(Theochem.)Analysis of the geometry of the hydroxymethyl radical by the "different hybrids for different spins" natural bond orbital procedure[J].1988,169,41-62.
[32](a)Ratner,M.Electronic motion in DNA Nature,1999,397,480-481.
(b)Jortner,J.;Bixon,J.;Langenbacher,M.;Michel-Beryede,T.Charge transfer and transport in DNA[J].Prec.Natl.Acad.Sci.U.S.A.1998,95,12759-12765.
[33](a)Liu,H.;Gao,J.;Lynch,S.R.;Saito,Y.D.;Maynard,L.;Keel,E.T.A Four-Base Paired Genetic Helix with Expanded Size[J].Science 2003,302,868-871.
(b)Gao,J.;Liu,H.;Keel,E.T.Expanded-Size Bases in Naturally Sized DNA:Evaluation of Steric Effects in Watson-Crick Pairing[J].J.Am.Chem.Soc.2004,126,11826-11831.
(c)Liu,H.;Gao,J.;Keel,E.T.Helix-Forming Properties of Size-Expanded DNA,an Alternative Four-Base Genetic Form[J].J.Am.Chem.Soc.2005,127,1396-1402.
(d)Liu,H.;Gao,J.;Keel,E.T.Size-Expanded Analogues of dG and dC:Synthesis and Pairing Properties in DNA[J].J.Org.Chem.2005,70,639-647.
[34]Deakyne,C.A.;Meot-Ner(Mautner),M.Unconventional ionic hydrogen bonds.2.NH~+…π Complexes of onium ions with olefins and benzene derivatives[J].J.Am.Chem.Soc.1985,107,474-479.
[35]Guo,B.C.;Pumell,J.W.;Casfleman Jr.,A.W.The clustering reactions of benzene with sodium and lead ions[J].Chem.Phys.Lett.1990,168,155-160.
[36]de Vos,A.M.;Ultshc,M.;Kossiakoff,A.A.Human growth hormone and extracellular domain of its receptor:crystal structure of the complex[J].Science 1992,255,306-312.
(1)Lee,A.G.Curr.Opin.Struct.Biol.2002,12,547.
(2)Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Nature 2000,405,647.
(3)Lee,A.G.;East,J.M.Biochem.J.2001,356,665.
(4)(a)Inesi,G.J.Biol.Chem.1987,262,16338;
(b)de Meis,L.The Sarcoplasmic Reticulum,Wiley,New York 1981.
(5)Sun,W.;Kinsel,G.R.;Marynick,D.S.J.Phys.Chem.A.1999,103,4113.
(6)Moussatova,A.;Vazquez,M.-V.;Martinez,A;Dolgounitcheva,O.;Zakrzewski,V.G.;Ortiz,J.V.;Pedersen,D.B.;Simard,B.J.Phys.Chem.A.2003,107,9415.
(7)Jensen,F.J.Am.Chem.Soc.1992,114,9533.
(8)Russo,N.;Toscano,M.;Grand,A.J.Am.Chem.Soc.2001,123,10272
(9)Russo,N.;Toscano,M.;Grand,A.J.Phys.Chem.A.2003,107,11533
(10)Hoyau,S.;Ohanessian,G.J.Am.Chem.Soc.1997,119,2016.
(11)Bertran,J.;Rodriguez-Santiago,L.;Sodupe,M.J.Phys.Chem.B.1999,103,2310.
(12)Marino,T.;Russo,N.;Toscano,M.J.Inorg.Biochem.2000,79,179.
(13)Remko,M.;Rode,B.M.Chem.Phys.Lett.2000,316,489.
(14)Moision,R.M.;Armentrout,P.B.J.Phys.Chem.A.2002,106,10350.
(15)Ai,H.;Bu,Y;Li,P.Int.J Quantum.Chem.2003,94,205.
(16)Corral,I.;Mo,O.;Yanez,M.;Scott,A.P.;Radom,L.J.Phys.Chem.A.2003,107,10456.
(17)Dunbar,R.C.J.Phys.Chem.A.2000,104,8067.
(18)Tsipis,A.C.;Tsipis,C.A.;Valla,V.J.Mol.Struct.(Theochem).2003,630,81.
(19)(a)Bouchonet,S.;Hoppilliard,Y.Org.Mass Spectrom.1992,27,71.
(b)Bouchonet,S.;Flament,J.P.;Hoppilliard,Y.Rapid Commun.Mass Spectrom.1993,7,470.
(20)Hoyau,S.;Ohanessian,G.Chem.Eur J.1998,4,1561.
(21)Wyttenbach,T.;Witt,M.;Bowers,M.T.Int.J.Mass Spectrom.2001,243,182.
(22)Pulkkinen,S.;Noguera,M.;Rodriguez-Santiago,L.;Sodupe,M.;Bertran,J.Chem.Eur.J.2000,6,4393.
(23)Strittmatter,E.F.;Lemoff,A.S.;Williams,E.R.J.Phys.Chem.A.2000,104,9793.
(24)Rulisek,L.;Havlas,Z.J.Am.Chem.Soc.2000,122,10428.
(25)(a)Becke,A.D.J.Chem.Phys.1993,98,5648.
(b)Lee,C.;Yang,W.;Parr,R.G.Phys.ReV.B 1988,37,785.
(c)Stevens,P.J.;Devlin,F.J.;Chablowski,C.F.;Frisch,M.J.J.Phys.Chem.1994,98.11623.
(26)Dudev,T.;Lim,C.J.Phys.Chem.B.2004,108,4546.
(27)Ban,F.;Kusalik,P.;Weaver,D.F.J.Am.Chem.Soc.2004,126,4711.
(28)CRC Handbook of Chemistry and Physics,82nd Edition(2001-2002).
(29)Frisch,M.J.;Del Bene,J.E.;Binkley,J.S.;Schaefer,H.F.,Ⅲ.J.Chem.Phys.1986,84,2279.
(30)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.;Dapprieh,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.;Maliek,D.K.;Rabuck,A.D.;Raghavaehari,K.;Foresrnan,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.;Challaeombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Andres,J.L.;Gonzalez,C.;Head-Gordon,M.;Replogle,E.S.;Pople,J.A.Gaussian 98,Revision A.9;Gaussian,Inc.;Pittsburgh PA,1998.
(1)Glynn,I.M.J.Physiol.1993,462,1.
(2)Drake,S.K.;Lee,K.L.;Falke,J.J.Biochem.1996,35,6697.
(3)Yau,W.M.;Wimley,W.C.;Gawrisch,K.;White,S.H.Biochem.1998,37,14713.
(4)Lee,A.G.;East,J.M.Biochem.d.2001,356,665.
(5)Toyoshima,C.;Nakasako,M.;Nomura,H.;Ogawa,H.Nature 2000,405,647.
(6)Frontera,A.;Quifionero,D.;Garau,C.;Costa,A.;Ballester,P.;Deya,P.M.J.Phys.Chem.A 2006,110,9307.
(7)(a)Felder,C.;Jiang,H.;Zhu,W.;Chen,K.;Silman,I.;Botti,S.A.;Sussman,J.L.J.Phys.Chem.A 2001,105,1326.
(b)Liu,T.;Zhu,W.;Gu,J.;Shen,J.;Luo,X.;Chen,G.;Puah,C.M.;Silman,I.;Chen,K.;Sussman,J.L.;Jiang,H.J.Phys.Chem.A 2004,108,9400.
(c)Tan.X.;Zhu,W.;Cui,M.;Luo,X.;Gu,J.;Silman,I.;Sussman,J.L.;Jiang,H.;Ji,R..;Chen,K.Chem.Phys.Lett.2001,349,113.
(8)(a)Dudev,T.;Lim,C.Acc.Chem.Res.2007,40,85.
(b)Dudev,T.;Lim,C.J.Am.Chem.Soc.2006,128,10541.
(9)Jensen,F.J.Am.Chem.Soc.1992,114,9533.
(10)(a)Hoyau,S.;Ohanessian,G.Chem.Eur.J.1998,4,1561.
(b)Hoyau,S.;Ohanessian,G.J.Am.Chem.Soc.1997,119,2016.
(11)Wyttenbach,T.;Witt,M.;Bowers,M.T.Int.J.Mass Spectrom.2001,243,182.
(12)Pulkkinen,S.;Noguera,M.;Rodri'guez-Santiago,L.;Sodupe,M.;Bertran,J.Chem.Eur.J.2000,6,4393.
(13)Bertran,J.;Rodriguez-Santiago,L.;Sodupe,M.J.Phys.Chem.B 1999,103,2310.
(14)Ma,J.C.;Dougherty,D.Chem.Rev.1997,97,1303.
(15)Ryahov,V.;Dunbar,R.C.J.Am.Chem.Soc.1999,121,2259.
(16)Jernigan,R.;Raghunathan,G.;Bahar,I.Curr.Opin.Struct.Biol.1994,4,256.
(17)Gouaux,E.;MacKinnon,R.Science 2005,310,1461.
(18)Frisch,M.J.;Trucks,G.W.;Schlegel,H.B.;Scuseria,G.E.;Robb,M.A.;Cheeseman,J.R.;Montgomery,J.A.,Jr.;Vreven,T.;Kudin,K.N.;Burant,J.C.;Millam,J.M.;Iyengar,S.S.;Tomasi,J.;Barone,V.;Mennucci,B.;Cossi,M.; Scalmani,G.;Rega,N.;Petersson,G.A.;Nakatsuji,H.;Hada,M.;Ehara,M.;Toyota,K.;Fukuda,R.;Hasegawa,J.;Ishida,M.;Nakajima,T.;Honda,Y.;Kitao,O.;Nakai,H.;Klene,M.;Li,X.;Knox,J.E.;Hratchian,H.P.;Cross,J.B.;Bakken,V.;Adamo,C.;Jaramillo,J.;G-omperts,R.;Stratmann,R.E.;Yazyev,O.;Austin,A.J.;Cammi,R.;Pomelli,C.;Ochterski,J.W.;Ayala,P.Y.;Morokuma,K.;Voth,G.A.;Salvador,P.;Dannenberg,J.J.;Zakrzewski,V.G.;Dapprich,S.;Daniels,A.D.;Strain,M.C.;Farkas,O.;Malick,D.K.;Rabuck,A.D.;Raghavachari,K.;Foresman,J.B.;Ortiz,J.V.;Cui,Q.;Baboul,A.G.;Clifford,S.;Cioslowski,J.;Stefanov,B.B.;Liu,G.;Liashenko,A.;Piskorz,P.;Komaromi,I.;Martin,R.L.;Fox,D.J.;Keith,T.;Al-Laham,M.A.;Peng,C.Y.;Nanayakkara,A.;Challacombe,M.;Gill,P.M.W.;Johnson,B.;Chen,W.;Wong,M.W.;Gonzalez,C.;Pople,J.A.Gaussian 03,revision B.05;Gaussian,Inc.:Wallingford,CT,2004.
(19)(a)Becke,A.D.J.Chem.Phys.1993,98,5648.
(b)Becke,A.D.Phys.Rev.1988,A38,3098.
(20)Lee,C.;Yang,W.;Parr,R.G.Phys.Rev.1988,B37,785.
(21)Becke,A.D.J.Chem.Phys.1993,98,1372.The BHandHLYP keyword in Gaussian employs a functional according to the formula,BHandHLYP:0.5×E_x(HF)+0.5×E_x(LSDA)+0.5×ΔE_x(Becke88)+E_c(LYP),which is not precisely the formulation proposed by A.D.Becke in his paper.
(22)Frisch,M.J.;Del Bene,J.E.;Binkley,J.S.;Schaefer,H.F.,Ⅲ.J.Chem.Phys.1986,84,2279.
(23)(a)Glendening,E.D.;Reed,A.E.;Carpenter,J.E.;Weinhold,F.NBO Version 3.1,
(b)Reed,A.E.;Curtiss,L.A.;Weinhold,F.Chem.Rev.1988,88,899.
(24)Breneman,C.M.;Wiberg,K.B.J.Comp.Chem.1990,11,361.
(25)CRC Handbook of Chemistry and Physws,82nd ed.;Lide,D.R.,Ed.;CRC Press:Cleveland,2001-2002.
(26)Marcus,Y.Chem.Rev.1988,88,1475.
(27)Alabugin,I.V.;Manoharan,M.;Peabody,S.;Weinhold,F.J.Am.Chem.Soc.2003,125,5973.
(28)de Vos,A.M.;Ultshc,M.;Kossiakoff,A.A.Science 1992,255,306.
(29)Pflugrath,J.W.;Wigand,G.;Huber,R.;Vertesy,L.J.Mol.Biol.1986,189,383.
(30)Rardin,R.L.;Tolmann,W.B.;Lippard,S.J.New J.Chem.1991,15,417.
(31)Rodriguez-Cruz,S.E.;Jockusch,R.A.;Williams,E.R.J.Am.Chem.Soc.1999,121,1986.
(32)Bezanilla,F.;Armstrong,C.M.d.Gen.Physiol.1972,60,588.
(33)Katz,A.K.;Glusker,J.P.;Beebe,S.A.;Bock,C.W.J.Am.Chem.Soc.1996,118,5752.
(34)(a)Falke,J.J.;Drake,S.K.;Hazard,A.L.;Peersen,O.B.Q.Rev.Biophys.1994,27,219.
(b)Drake,S.K.;Zimmer,M.A.;Kundrot,C.;Falke,J.J.J.Gen.Physiol.1997,110,173.
(c)Drake,S.K.;Zimmer,M.A.;Miller,C.L.;Falke,J.J.Biochemistry 1997,36,9917.
(35)Nonner,W.;Catacuzzeno,L.;Eisenberg,B.Biophys.J.2000,79,1976.
(36)Boda,D.;Busath,D.;Henderson,D.Sokolowsld,S.J.Phys.Chem.B 2000,104,8903.
(37)(a)Cony,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.Biochim.Biophys.Acta 2000,1509,1.
(b)Corry,B.;Allen,T.W.;Kuyucak,S.;Chung,S.H.Biophys.J.2001,80,195.
(c)Corry,B.;Vora,T.;Chung,S.H.Biochim.Biophys.Acta 2005,1711,72.
(d)Cony,B.;Chung,S.H.Cell.Mol.Life Sci.2006,63,301.
(38)Dudev,M.;Wang,J.;Dudev,T.;Lim,C.J.Phys.Chem.B 2006,110,1889.
(39)Dobler,M.Ionophores and Their Structures;Wiley:New York,1981.