几类重要蛋白质的分子动力学模拟及相关抑制剂的改良
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摘要
本文利用同源模建、分子对接、分子动力学等方法,对人类肺表面活性蛋白D(hSP-D)、人类胞外信号调节激酶1(hERK1)和人类碳酸酐酶VII(hCA VII)三种重要的蛋白质进行了深入的理论研究,主要内容包括:
1.利用拉伸分子动力学方法研究了三种单糖脱离hSP-D结合位点的过程,分析了该过程中hSP-D和单糖之间的相互作用,探索了脱离过程中特殊的非平衡性质的成因。结果表明,hSP-D结合位点处残基Glu321、Asn323、Asp325、Glu329和Arg343是导致单糖脱离非平衡性质的关键残基。三种单糖不同的羟基取向与结合方式也导致了它们非平衡性质的差别。
2.利用同源模建和分子动力学方法构建了hERK1的三维结构,然后进行两种已知抑制剂的对接与结构改良。结果表明,它们与酶的结合方式相似。取代基的不同导致了抑制能力的差别。改良抑制剂在保持与Lys36和Gln87氢键的同时,又与残基Asp93, Lys96, Ser135形成了四条氢键。对接相互作用能和MM/PBSA结合自由能的下降证明其抑制能力的增强。
3.利用同源模建、分子对接和分子动力学方法研究了一个已知抑制剂对hCA II和hCA VII的选择性机理,并对其做了结构改良。结果表明,该抑制剂的选择性是由hCA II的Asn67和hCA VII的Gln64支链长度不同引起的。Gln64支链多了一个亚甲基,使得它能与已知抑制剂中的溴原子形成氢键。而改良抑制剂增加了羟丙基,该基团与hCA VII的残基Gln64形成了氢键。MM/PBSA结合自由能的计算验证了改良抑制剂选择性的提高。
Today, along with the development of the relative theories and the advancement of computer technology, the molecular simulations of protein have been an important research field in biology science. Homology modeling, molecular docking and molecular dynamics methods can be used to theoretically construct the three dimension structure of protein and to study the interaction between ligand and receptor. On this basis, the obtained results can give the explanation of the experimental phenomenon and provide the theoretical guidance for the inhibitor design of the special protein and the development of the new drug for the related diseases. In the thesis, these methods were used to study three kinds of important proteins. The main results are summarized as follows:
1. Dynamic interaction between human pulmonary surfactant protein D (hSP-D) and monosaccharides
Human pulmonary surfactant protein D (hSP-D) is a kind of important protein in human lung innate immune system. It binds to surface carbohydrates on all kinds of inhaled pathogens and particles, facilitating their uptake and clearance by other innate immune cell. Hence the protein is involved in many diseases, including influenza and HIV etc. The latest researches show that the dynamic interaction between the protein and monosacchrides is different from the quality in the stable state. The cause is unclear.
Molecular docking, conventional molecular dynamics and steered molecular dynamics were used to study the dissociation of three monosaccharides from hSP-D and analyze the special dynamic interaction during the process. Then the adaptive biasing force (ABF) method was used to compute the free energy profile of dissociation. The results show that three monosacchrides have the different transition state energy values in the dissociation, resulting to their different energy barrier. The check in the atomic level gives the different conformation in the transition state. The residues Glu321, Asn323, Asp325, Glu329 and Arg343 are responsible for the non-equilibrium nature. The different directions of OH groups in the monosaccharides result in their different dynamic interaction with hSP-D. The OH groups in C3 and C4 carbon atoms of glucose form H-bonds with Glu321, Asn323 and Glu329. But the other OH groups have little influence on the non-equilibrium affinity. The different binding mode of galactose is different from the other two monosaccharides, attributing to its non-equilibrium quality. The monosaccharide forms H-bonds with thre residue Glu321 by the OH groups in its C1 and C2 carbon atoms. Because C1 carbon atom is its anomeric carbon atom, its anomer influences its non-equilibrium quality. Mannose and glucose have the similar binding mode. Their differences are caused by the H-bond between Asp325 and the OH group in the C2 atom of mannose during the unbinding process. The H-bond pulls mannose forward Glu329 and Arg343, forming another three H-bonds by the OH groups in the C3, C4 and C6 carbon atoms, increasing the energy barrier. The result is that the monosaccharide shows the different dissociation quality. This work could provide the more penetrating understanding of hSP-D physiological functions.
2. Homology Modeling of Human Extracellular Signal-regulated Kinase 1 (hERK 1) and Docking and Reconstitution of its Inhibitors
The extracellular signal-regulated kinases are the important componet of the Ras/Raf/MEK/ERK signal transduction pathway, which is highly preserved in all the eukaryotic cells and controls a variety of fundamental cellular processes including cell survival, proliferation, motility, differentiation and metabolism. Hence it is involved in the development of new drug for cancer and inflammatory diseases.
The three dimensional structure of hERK1 was modeled and refined using homology modeling and molecular dynamics simulations. Then docking and reconstruction of the inhibitors were carried out. The MM/PBSA approach and two kinds of docking interaction energies were used to evaluate the potency of the inhibitors. The results show that the two inhibitors share the same binding pattern, interacting with Lys36 and Gln87 by H-bonds. Their different substituent groups lead to the different affinities with hERK1. Based on the analysis, the modification for one inhibitor was carried out by the addition of new groups. The new inhibitor reserves the H-bonds at the same time to form four H-bonds with Asp93, Lys96 and Ser135, significantly increasing the interaction with hERK1. The two docking energies significantly decrease, even the binding free energy of MM/PBSA decreases to be the negative value, proving the raise of inhibiting capacity. This work provided the theoretical guidance for the inhibitor design of hERK1 and the development of the new drug for the related diseases.
3. Theoretical design of the specific inhibitor of human carbonic anhydrase VII
In mammals, carbonic anhydrases (CAs) are ubiquitous zinc-metalloenzymes that catalyze a very simple but important physiological reaction, the interconversion between carbon dioxide and the bicarbonate ion. Hence these zinc enzymes are involved in a number of important physiological processes such as respiration and gas exchange, pH homeostasis, cell proliferation and differentiation, etc. The very different distribution of all kinds of isoforms in various tissues and organs as well as quite diverse catalytic properties may be the most prominent reason for unwanted side effects resulting from systemic administration of many nonspecific broad spectrum CA inhibitors. Hence the design of tissue-selective and isozyme-specific inhibitors becomes a critical solution in the chemistry and biology of the carbonic anhydrases.
The selectivity of a known inhibitor for hCA II and hCA VII was studied by homology modeling, molecular docking and molecular dynamics methods. The modification for the inhibitor was performed. The MM/PBSA approach was used to evaluate the potency of the inhibitors. The results show that the selectivity of the inhibitor for two isozymes is due to the different side chain length between Asn67 of hCA II and Gln64 of hCA VII. One more methene group in the side chain of Gln64 of hCA VII makes it possible to form H-bond with the bromide atom in the inhibitor. Such the H-bond doesn’t exist between hCA II and the kown inhibitor because of the longer distance. On the basis of the analysis, the modification was carried out by the addition of the hydroxypropyl group. The complex conformations of the new inhibitor and two isozymes designate the formation of the H-bond between the newly-added group and Gln64 of hCA VII but not Asn67 of hCA II. The results obtained from the MM/PBSA approach show the binding free energy between the new inhibitor and hCA II has the minor change but that for hCA VII decrease, which increase the selectivity of the new inhibitor for two isoforms. The work will help the design of the isozyme-specific inhibitors of hCA VII.
1.利用拉伸分子动力学方法研究了三种单糖脱离hSP-D结合位点的过程,分析了该过程中hSP-D和单糖之间的相互作用,探索了脱离过程中特殊的非平衡性质的成因。结果表明,hSP-D结合位点处残基Glu321、Asn323、Asp325、Glu329和Arg343是导致单糖脱离非平衡性质的关键残基。三种单糖不同的羟基取向与结合方式也导致了它们非平衡性质的差别。
2.利用同源模建和分子动力学方法构建了hERK1的三维结构,然后进行两种已知抑制剂的对接与结构改良。结果表明,它们与酶的结合方式相似。取代基的不同导致了抑制能力的差别。改良抑制剂在保持与Lys36和Gln87氢键的同时,又与残基Asp93, Lys96, Ser135形成了四条氢键。对接相互作用能和MM/PBSA结合自由能的下降证明其抑制能力的增强。
3.利用同源模建、分子对接和分子动力学方法研究了一个已知抑制剂对hCA II和hCA VII的选择性机理,并对其做了结构改良。结果表明,该抑制剂的选择性是由hCA II的Asn67和hCA VII的Gln64支链长度不同引起的。Gln64支链多了一个亚甲基,使得它能与已知抑制剂中的溴原子形成氢键。而改良抑制剂增加了羟丙基,该基团与hCA VII的残基Gln64形成了氢键。MM/PBSA结合自由能的计算验证了改良抑制剂选择性的提高。
Today, along with the development of the relative theories and the advancement of computer technology, the molecular simulations of protein have been an important research field in biology science. Homology modeling, molecular docking and molecular dynamics methods can be used to theoretically construct the three dimension structure of protein and to study the interaction between ligand and receptor. On this basis, the obtained results can give the explanation of the experimental phenomenon and provide the theoretical guidance for the inhibitor design of the special protein and the development of the new drug for the related diseases. In the thesis, these methods were used to study three kinds of important proteins. The main results are summarized as follows:
1. Dynamic interaction between human pulmonary surfactant protein D (hSP-D) and monosaccharides
Human pulmonary surfactant protein D (hSP-D) is a kind of important protein in human lung innate immune system. It binds to surface carbohydrates on all kinds of inhaled pathogens and particles, facilitating their uptake and clearance by other innate immune cell. Hence the protein is involved in many diseases, including influenza and HIV etc. The latest researches show that the dynamic interaction between the protein and monosacchrides is different from the quality in the stable state. The cause is unclear.
Molecular docking, conventional molecular dynamics and steered molecular dynamics were used to study the dissociation of three monosaccharides from hSP-D and analyze the special dynamic interaction during the process. Then the adaptive biasing force (ABF) method was used to compute the free energy profile of dissociation. The results show that three monosacchrides have the different transition state energy values in the dissociation, resulting to their different energy barrier. The check in the atomic level gives the different conformation in the transition state. The residues Glu321, Asn323, Asp325, Glu329 and Arg343 are responsible for the non-equilibrium nature. The different directions of OH groups in the monosaccharides result in their different dynamic interaction with hSP-D. The OH groups in C3 and C4 carbon atoms of glucose form H-bonds with Glu321, Asn323 and Glu329. But the other OH groups have little influence on the non-equilibrium affinity. The different binding mode of galactose is different from the other two monosaccharides, attributing to its non-equilibrium quality. The monosaccharide forms H-bonds with thre residue Glu321 by the OH groups in its C1 and C2 carbon atoms. Because C1 carbon atom is its anomeric carbon atom, its anomer influences its non-equilibrium quality. Mannose and glucose have the similar binding mode. Their differences are caused by the H-bond between Asp325 and the OH group in the C2 atom of mannose during the unbinding process. The H-bond pulls mannose forward Glu329 and Arg343, forming another three H-bonds by the OH groups in the C3, C4 and C6 carbon atoms, increasing the energy barrier. The result is that the monosaccharide shows the different dissociation quality. This work could provide the more penetrating understanding of hSP-D physiological functions.
2. Homology Modeling of Human Extracellular Signal-regulated Kinase 1 (hERK 1) and Docking and Reconstitution of its Inhibitors
The extracellular signal-regulated kinases are the important componet of the Ras/Raf/MEK/ERK signal transduction pathway, which is highly preserved in all the eukaryotic cells and controls a variety of fundamental cellular processes including cell survival, proliferation, motility, differentiation and metabolism. Hence it is involved in the development of new drug for cancer and inflammatory diseases.
The three dimensional structure of hERK1 was modeled and refined using homology modeling and molecular dynamics simulations. Then docking and reconstruction of the inhibitors were carried out. The MM/PBSA approach and two kinds of docking interaction energies were used to evaluate the potency of the inhibitors. The results show that the two inhibitors share the same binding pattern, interacting with Lys36 and Gln87 by H-bonds. Their different substituent groups lead to the different affinities with hERK1. Based on the analysis, the modification for one inhibitor was carried out by the addition of new groups. The new inhibitor reserves the H-bonds at the same time to form four H-bonds with Asp93, Lys96 and Ser135, significantly increasing the interaction with hERK1. The two docking energies significantly decrease, even the binding free energy of MM/PBSA decreases to be the negative value, proving the raise of inhibiting capacity. This work provided the theoretical guidance for the inhibitor design of hERK1 and the development of the new drug for the related diseases.
3. Theoretical design of the specific inhibitor of human carbonic anhydrase VII
In mammals, carbonic anhydrases (CAs) are ubiquitous zinc-metalloenzymes that catalyze a very simple but important physiological reaction, the interconversion between carbon dioxide and the bicarbonate ion. Hence these zinc enzymes are involved in a number of important physiological processes such as respiration and gas exchange, pH homeostasis, cell proliferation and differentiation, etc. The very different distribution of all kinds of isoforms in various tissues and organs as well as quite diverse catalytic properties may be the most prominent reason for unwanted side effects resulting from systemic administration of many nonspecific broad spectrum CA inhibitors. Hence the design of tissue-selective and isozyme-specific inhibitors becomes a critical solution in the chemistry and biology of the carbonic anhydrases.
The selectivity of a known inhibitor for hCA II and hCA VII was studied by homology modeling, molecular docking and molecular dynamics methods. The modification for the inhibitor was performed. The MM/PBSA approach was used to evaluate the potency of the inhibitors. The results show that the selectivity of the inhibitor for two isozymes is due to the different side chain length between Asn67 of hCA II and Gln64 of hCA VII. One more methene group in the side chain of Gln64 of hCA VII makes it possible to form H-bond with the bromide atom in the inhibitor. Such the H-bond doesn’t exist between hCA II and the kown inhibitor because of the longer distance. On the basis of the analysis, the modification was carried out by the addition of the hydroxypropyl group. The complex conformations of the new inhibitor and two isozymes designate the formation of the H-bond between the newly-added group and Gln64 of hCA VII but not Asn67 of hCA II. The results obtained from the MM/PBSA approach show the binding free energy between the new inhibitor and hCA II has the minor change but that for hCA VII decrease, which increase the selectivity of the new inhibitor for two isoforms. The work will help the design of the isozyme-specific inhibitors of hCA VII.
引文
[1] YOCKEY H P, PLATZMAN R P, QUASTLER H. Symposium on Information Theory in Biology [C]. Pergamon Press, New York, London, 1958.
[2]张春霆.生物信息学的现状与展望[J].世界科技研究与发展, 2000, 22(6):17-20.
[3]王正华,王勇献.后基因组时代生物信息学的新进展[J].国防科技大学学报,2003, 25(1):1-6.
[4] CALIFANO A. Advances in Sequence Analysis [J]. Current Opinion in Structural Biology, 2002, 11(3):330-333.
[5] KUNDU A, BAYYA A. Speech Recognition Using Bybrid Hidden Markov Model and NN Classifier [J]. International Journal of Speech Technology, 1998, 2(3):227-240.
[6]郑珂晖.生物信息学的背景、现状及前景[J].农业网络信息, 2005, (2):4-7.
[7]陈润生.生物信息学及其研究进展[J].医学研究通讯, 2002, 31(12):2-5.
[8]王发生,毛君莲.生命科学时代的生物信息学[J].中国现代医学杂志, 2000, 10(12):108-109.
[9]赵南明,周海梦,等.生物物理学[M].北京:高等教育出版社,2000.
[10] CHUNG V, WAKEFIELD A E, KINSMAN O S, et al. DNA amplification of a portion of the phosphomannose isomerase (PMI) gene in Pneumocystis carinii-enriched extracts [J]. Journal of Eukaryotic Microbiology, 1994, 41:82S-83S.
[11] MCCAMMON J A, GELIN B R, KARPLUS M. Dynamics of folded proteins [J]. Nature, 1977, 267:585-590.
[12] WELLS T N, PAYTON M A, PROUDFOOT A E. Inhibition of phosphomannose isomerase by mercury ions [J]. Biochemistry, 1994, 33:7641-7646.
[13] GONEN T, CHENG Y, SLIZ P, et al. Lipid-protein interactions in double-layered two-dimensional AQP0 crystals [J]. Nature, 2005, 438:633-638.
[14] WELLS T N, SCULLY P, MAGNENAT E. Arginine 304 is an active site residue in phosphomannose isomerase from Candida albicans [J]. Biochemistry, 1994,
[44] BEN-TAL N, SITKOFF D, BRANSBURG-ZABARY S, et al. Theoretical calculations of the permeability of monensin-cation complexes in model bio-membranes [J]. Biochimica et biophysica acta, 2000, 1466: 221-233.
[45] SIVOZHELEZOV V, NICOLINI C, KARPINSKI S, et al. Toward a blueprint for UDP-glucose pyrophosphorylase structure/function properties: homology-modeling analyses [J]. Plant Molecular Biology, 2004, 56:783-794.
[46] LEE K W, BRIGGS J M. Molecular modeling study of the editing active site of Escherichia coli leucyl-tRNA synthetase: two amino acid binding sites in the editing domain [J]. Proteins, 2004, 54:693-704.
[47] ROY S, SEN S. Homology Modeling Based Solution Structure of Hoxc8-DNA Complex: Role of Context Bases Outside TAAT Stretch [J]. Journal of Biomolecular Structure & Dynamics, 2005, 22: 707-718.
[48] ROHL C A, STRAUSS C E, CHIVIAN D, et al. Modeling structurally variable regions in homologous proteins with rosetta [J]. Proteins, 2004, 55: 656-677.
[49] Chothia C. One thousand families for the molecular biologist [J]. Nature, 1992, 357:543-544.
[50] Wang Z X. A re-estimation for the total numbers of protein folds and superfamilies [J]. Protein Engineering, 1998, 11(8):621-626.
[51] THOMAS P D, DILL K A. An iterative method for extracting energy-like quantities from protein structures [J]. Proceedings of the National Academy of Sciences of the United States of America, 1996, 93(21):11628-11633.
[52] LATHROP R H, SMITH T F. Global optimum protein threading with gapped alignment and empirical pair score functions [J]. Journal of Molecular Biology, 1996, 255(4):641-665.
[53] FISCHER D, EISENBERG D. Protein fold recognition using sequence-derived predictions [J]. Protein Science, 1996, 5(5):947-955.
[54] STERNBERG M J, BATES P A, KELLEY L A, MACCALLUM R M. Progress in protein structure prediction: assessment of CASP3 [J]. Current Opinion in Structural Biology, 1999, 9(3):368-373.
[55] HOLLAND J H. Adaptation in Natural and Artificial Systems [M]. Ann Arbor,Boston: The University of Michigan Press, 1975.
[56]解伟,王翼飞.蛋白质折叠的三维计算机模拟[J].上海大学学报(自然科学版), 2000, 6(2):145-149.
[57] B?HM H J, KLEBE G. What can we learn from molecular recognition in protein-ligand complexes for the design of new drugs? [J]. Angew Chem Int Ed Engl, 1996, 35(22):2588-2614.
[58]张阳德.生物信息学(5):药物设计与生物信息学[J].外科理论与实践, 2007, 12(2):附41-附47.
[59]陈凯先.计算机辅助药物设计:原理、方法及应用[M].上海:上海科学技术出版社, 2000.
[60]李亮助,孙强明.生物信息学在药物设计中的应用[J].生命的化学, 2003, 23(5):364-366.
[61]郑彦,吕莉.计算机辅助药物设计在药物合成中的应用[J].齐鲁药事, 2008, 27(10):614-616.
[62]赵金城,王庆莉,毕秀玲.计算机辅助直接药物分子设计[J].大连大学学报,2002, 23(6):22-30.
[63] B?HM H J. LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads [J]. J Comput Aided Mol Des, 1992, 6(1):593-606.
[64] STERNBERG M J E. Protein structure prediction-a piratical approach Oxford: Oxford Press, 1996.
[65] BLUNDELL T L, CARNEY D, GARDNER S, et al. Knowledge-based protein modelling and design [J]. European Journal of Biochemistry, 1988, 172:513-520.
[66] SANCHEZ R, SALI A. Comparative protein structure modeling in genomics [J]. Journal of Computational Physics, 1999, 151(1): 388-401.
[67] SALI A, OVERINGTON J P, JOHNSON M S, et al. From comparisons of protein sequences and structures to protein modeling and design [J]. Trends in Biochemical Sciences, 1990, 15(6): 235-240.
[68] BLUNDELL T L, SIBANDA B L, STERNBERG M J E, et al. Knowledge-based prediction of protein structures and the design of novel molecules [J]. Nature, 1987, 326: 347-352.
[69]张漫,常延琦.蛋白质三级结构预测方法简述[J].中国动物检疫, 2005, 22(5):36-37.
[70]来鲁华等.蛋白质的结构预测与分子设计[M].北京大学出版社, 1993.
[71] NEEDLEMAN S B, WUNSCH C D. A general method applicable to search for similarities in the amino acid sequence of two proteins [J]. Journal of Molecular Biology, 1970, 48(3): 443-453.
[72] SMITH T F, WATERMAN M S. Identification of common molecular subsequences [J]. Journal of Molecular Biology, 1981, 147(1):195-197.
[73] LIPMAN D J, PEARSON W R. Rapid and sensitive protein similarity searches [J]. Science, 1985, 227:1435-1441.
[74] PEARSON W R, LIPMAN D J. Improved tools for biological sequence comparison [J]. Proc Natl Acad Sci USA, 1988, 85(8):2444-2448.
[75] ALTSCHUL S F, GISH W, MILLER W, MYERS E W, LIPMAN D J. Basic local alignment search tool [J]. Journal of Molecular Biology, 1990, 215(3):403-410.
[76] ALTSCHUL S F, GISH W. Local alignment statistics [J]. Methods Enzymol, 1996, 266:460-480.
[77] FENG D, DOOLITTLE R F. Progressive sequence alignment as a pre-requisite to correct phylogenetic trees [J]. J Mol Evol, 1987, 60:351-360.
[78] ANDREW R L. Molecular Modeling: Principles and Applications, 1996, Addison Wesley Longman Limited, London
[79] KAO J, ALLINGER N L. Conformational analysis. 122. Heats of formation of conjugated hydrocarbons by the force field method [J]. Journal of the American Chemical Society, 1977, 99(4): 975-986.
[80] ALLINGER N L, YAN L Q. Molecular mechanics (MM3). Calculations of furan, vinyl ethers, and related compounds [J]. Journal of the American Chemical Society, 1993, 115(25):11918-11925.
[81] ALLINGER N L, CHEN K, LII J H. An improved force field (MM4) for saturated hydrocarbons [J]. Journal of Computational Chemistry, 1996, 17(5):642-668.
[82] NEVINS N, CHEN K, ALLINGER N L. Molecular mechanics (MM4)calculations on alkenes [J]. Journal of Computational Chemistry, 1996, 17(5):669-694.
[83] HALGREN T A. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 [J]. Journal of Computational Chemistry, 1996, 17(5):490-519.
[84] HALGREN T A, NACHBAR R B. Merck molecular force field. IV. conformational energies and geometries for MMFF94 [J]. Journal of Computational Chemistry, 1996, 17(5):587-615.
[85] WEINER S J, KOLLMAN P A, NGUYEN D T, CASE D A. An all atom force field for simulations of proteins and nucleic acids [J]. Journal of Computational Chemistry, 1986, 7(2): 230-252.
[86] WEINER S J, KOLLMAN P A, CASE D A, SINGH U C, GHIO C, ALAGONA G, PROFETA S, WEINER P. A new force field for molecular mechanical simulation of nucleic acids and proteins [J]. Journal of the American Chemical Society, 1984, 106(3):765-784.
[87] CORNELL W D, CIEPLAK P, BAYLY C I, GOULD I R, MERZ K M, FERGUSON D M, SPELLMEYER D C, FOX T, CALDWELL J W, KOLLMAN P A. A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules [J]. Journal of the American Chemical Society, 1995, 117(19):5179-5197.
[88] BROOKS B R, BRUCCOLERI R E, OLAFSON B D, STATES D J, SWAMINATHAN S, KARPLUS M. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations [J]. Journal of Computational Chemistry, 1983, 4(2): 187-217.
[89] MOMANY F A, RONE R. Validation of the general purpose QUANTA ?3.2/CHARMm? force field [J]. Journal of Computational Chemisty, 1992, 13: 888-900.
[90] MACKERELL A D, JR, WIORKIEWICZ-KUCZERA J, KARPLUS M. An all-atom empirical energy function for the simulation of nucleic acids [J]. Journal of the American Chemical Society, 1995, 117(48):11946-11975.
[91] MACKERELL A D, JR, BASHFORD D, BELLOTT M, et al. All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins [J] Journal of Physical Chemistry B, 1998, 102(18):3586-3616.
[92] HAGLER A T, HULER E, LIFSON S. Energy functions for peptides and proteins. I. Derivation of a consistent force field including the hydrogen bond from amide crystals [J]. Journal of the American Chemical Society, 1974, 96(17): 5319-5327.
[93] HAGLER A T, LIFSON S. Energy functions for peptides and proteins. II. Amide hydrogen bond and calculation of amide crystal properties [J]. Journal of the American Chemical Society, 1974, 96(17): 5327-5335.
[94] LIFSON S, HAGLER A T, DAUBER P. Consistent force field studies of intermolecular forces in hydrogen-bonded crystals. 1. Carboxylic acids, amides, and the C:O.cntdot..cntdot..cntdot.H- hydrogen bonds [J] Journal of the American Chemical Society, 1979, 101(18): 5111-5121.
[95] HAGLER A T, LIFSON S, DAUBER P. Consistent force field studies of intermolecular forces in hydrogen-bonded crystals. 2. A benchmark for the objective comparison of alternative force fields [J] Journal of the American Chemical Society, 1979, 101(18): 5122-5130.
[96] HAGLER A T, DAUBER P, LIFSON S. Consistent force field studies of intermolecular forces in hydrogen-bonded crystals. 3. The C:O.cntdot..cntdot..cntdot.H-O hydrogen bond and the analysis of the energetics and packing of carboxylic acids [J]. Journal of the American Chemical Society, 1979, 101(18): 5131-5141.
[97] KITSON D H, HAGLER A T. Theoretical studies of the structure and molecular dynamics of a peptide crystal [J] Biochemistry, 1988, 27(14):5246-5257.
[98] KITSON D H, HAGLER A T. Catalysis of a rotational transition in a peptide by crystal forces [J]. Biochemistry, 1988, 27(19): 7176-7180.
[99] DAUBER-OSGUTHORPE P, ROBERTS V A, OSGUTHORPE D J, WOLFF J, GENEST M, HAGLER A T. Structure and energetics of ligand binding to proteins: Escherichia coli dihydrofolate reductase-trimethoprim, a drug-receptor system [J] Proteins: Structure, Function, and Genetics, 1988, 4(1):31-47.
[100] MAPLE J R, HWANG M J, STOCKFISCH T P, DINUR U, WALDMAN M, EWIG C S, HAGLER A T. Derivation of class II force fields. I. Methodology and quantum force field for the alkyl functional group and alkane molecules [J] Journal of Computational Chemistry, 1994, 15(2):162-182.
[101] MAPLE J R, DINUR U, HAGLER A T. Derivation of force fields for molecular mechanics and dynamics from ab initio energy surfaces [J]. Proc. Nat. Acad. Sci. USA, 1988, 85(15):5350-5354.
[102] HWANG M J, STOCKFISCH T P, HAGLER A T. Derivation of Class II Force Fields. 2. Derivation and Characterization of a Class II Force Field, CFF93, for the Alkyl Functional Group and Alkane Molecules [J]. Journal of the American Chemical Society, 1994, 116(6): 2515-2525.
[103] MAPLE J R, HWANG M J, JALKANEN K J, STOCKFISCH T P, HAGLER A T. Derivation of class II force fields: V. Quantum force field for amides, peptides, and related compounds [J]. Journal of Computational Chemistry, 1998, 19(4):430-458.
[104] SUN H, MUMBY S J, MAPLE J R, HAGLER A T. An ab Initio CFF93 All-Atom Force Field for Polycarbonates [J]. Journal of the American Chemical Society, 1994, 116(7): 2978-2987.
[105] SUN H, MUMBY S J, MAPLE J R, HAGLER A T. Ab Initio Calculations on Small Molecule Analogs of Polycarbonates [J]. Journal of Physical Chemistry, 1995, 99(16): 5873-5882.
[106] SUN H. Ab initio calculations and force field development for computer simulation of polysilanes [J]. Macromolecules, 1995, 28(3):701-712.
[107] SUN H. Ab initio characterizations of molecular structures, conformation energies, and hydrogen-bonding properties for polyurethane hard segments [J]. Macromolecules, 1993, 26(22):5924-5936.
[108] PAPPE A K, CASEWIT C J, COLWELL K S, et al. UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations [J]. Journal of the American Chemical Society, 1992, 114 : 10024-10035.
[109] MAYO S L, OLAFSON B D, GODDARD W A. DREIDING: A Generic ForceField for Molecular Simulations [J]. Journal of Physical Chemistry, 1990, 94: 8897-8909.
[110] BUNTE S W. Molecular Modeling of Energetic Materials: The Parameterization and Validation of Nitrate Esters in the COMPASS Force Field [J]. Journal of Physical Chemistry B, 2001, 104, 2477-2489.
[111] CASEWIT C J, COLWELL K S, RAPPE A K. Application of a universal force field to organic molecules [J]. Journal of the American Chemical Society, 1992, 114, 10035-10046.
[112] ROSENTHAL A B, GAROFALINI S H. Molecular dynamics of amorphous titanium silicate [J]. Journal of Non-Crystalline Solids, 1988, 107, 65-72.
[113] KOHLER A E, GAROFALINI S H. Effect of Composition on the Penetration of Inert Gases Adsorbed onto Silicate Glass Surfaces [J]. Langmuir, 1994, 10, 4664-4669.
[114] LEVITT M, LIFSON S. Refinement of protein conformations using a macromolecular energy minimization procedure [J]. Journal of Molecular Biology, 1969, 46, 269-279.
[115] FLECHER R, REEVES C M. Function minimization by conjugate gradients [J]. The Computer Journal, 1964, 7, 149-154.
[116] FLECHER R. Practical Methods of Optimization, Vol. 1, Unconstrained Optimization, 1980, John Wiley & Sons, New York.
[117] POWELL M J D. Restart procedures for the conjugate gradient method [J]. Mathematical Programming, 1977, 12, 241-254.
[118] GUNSTEREN W F, KARPLUS M. A method for constrained energy minimization of macromolecules [J]. Journal of Computationl Chemistry, 1980, 1, 266-274.
[119] BROYDEN C G. The Convergence of a Class of Double-rank Minimization Algorithms [J]. Journal of International Mathematical. Application, 1970, 6, 222-231
[120] FLECHER R. A new approach to variable metric algorithms [J]. The Computer Journal, 1970, 13, 317-322.
[121] GOLDFARB, D. A Family of Variable Metric Updates Derived by Variational Means [J]. Mathematics of Computing, 1970, 24, 23-26.
[122] SHANNO, D. F. Conditioning of Quasi-Newton Methods for Function Minimization [J]. Mathematics of Computing, 1970, 24, 647-656.
[123] FERMI E, PASTA J, ULAM S. Collected Papers of Enrico Fermi. Edited by Segre E. Chicago: University of Chicago Press, 1965.
[124] ALDER B J, WAINWRIGHT T E. Studies in Molecular Dynamics. I. General Method [J]. Journal of Chemical Physics, 1959, 31, 459-467.
[125] RAHMAN A. Correlations in the Motion of Atoms in Liquid Argon [J]. Physical Review, 1964, 136: A405-A411.
[126] VERLET L. Computer "Experiments" on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules [J]. Physcal Review, 1967, 159: 98-103.
[127] DUAN Y, KOLLMAN P A. Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution [J]. Science, 1998, 282: 740-744.
[128] ZHONG Q, JIANG Q, MOORE P B, et al. Molecular dynamics simulation of a synthetic ion channel [J]. Biophysical Journal, 1998, 74: 3-10.
[129] ZHONG Q, MOORE P B, NEWNS D M, et al. Molecular dynamics study of the LS3 voltage-gated ion channel [J]. FEBS Letter, 1998, 427: 267-270.
[130] MI H, TUCKERMAN M E, SCHUSTER D I, et al. A molecular dynamics study of HIV-1 protease complexes with C60 and fullerene-based anti-viral agents [J]. Proceedings of the Electrochemical Society, 1999, 99, 256-269.
[131] TUCKERMAN M E, MARTYNA G. J. Understanding Modern Molecular Dynamics: Techniques and Applications [J]. Journal of Physics Chemistry B, 2000, 104: 159-178.
[132] BEEMAN D. Some Multistep Methods for Use in Molecular Dynamics Calculations [J]. Journal of Computational Chemistry, 1976, 20, 130-139.
[133] VERLET L. Computer "Experiments" on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules [J]. Physical Review, 1963, 159: 98-103.
[134] HOOVER W G. Canonical dynamics: Equilibrium phase-space distributions [J]. Physical Review A, 1985, 31: 1695-1697.
[135] NOSE S, KLEIN M L. Constant pressure molecular dynamics for molecular systems [J]. Molecular Physics, 1983, 50: 1055-1076.
[136] NOSE S. A molecular dynamics method for simulations in the canonical ensemble [J]. Molecular Physics, 1984, 53: 255-268.
[137] NOSE S, YONEZAWA F. Isothermal–isobaric computer simulations of melting and crystallization of a Lennard-Jones system [J]. Journal of Chemical Physics, 1986, 84: 1803-1815.
[138] HAILE J M, GRABEN H W. Molecular dynamics simulations extended to various ensembles. I. Equilibrium properties in the isoenthalpic–isobaric ensemble [J]. Journal of Chemical Physics, 1980, 73: 2412-2420.
[139]徐筱杰.计算机辅助药物分子设计[M].北京:化学工业出版社,2004.
[140] KUNTZ I D. Structure-based strategies for drug design and discovery [J]. Science, 257, 1992: 1078-1082.
[141] KUNTZ I D, AGARD D A. Assessment of the role of computations in structural biology [J]. Advance in Protein Chemistry, 2003, 66: 1-25.
[142] MENG E C, GSCHWEND D A, BLANEY J M, et al. Orientational sampling and rigid-body minimization in molecular docking [J]. Proteins, 1993, 17: 266-278.
[143] MORRIS G. M, GOODSELL D S, HUEY R, et al. Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4 [J]. Journal of Computational Aided Molecular Design, 1996, 10: 293-304.
[144] GOODSELL D S, OLSON A J. Automated docking of substrates to proteins by simulated annealing [J]. Proteins, 1990, 8: 195-202.
[145] OSTERBERG F, MORRIS G. M, SANNER M F, et al. Automated docking to multiple target structures: incorporation of protein mobility and structural water heterogeneity in AutoDock [J]. Proteins, 2002, 46: 34-40.
[146] KION A E, GLICK M, THOMA M, et al. Finding more needles in the haystack: A simple and efficient method for improving high-throughput docking results[J]. Journal of Medicinal Chemistry, 2004, 47: 2743-2749.
[147] LUTY B A, WASSERMAN Z R, STOUTEN P F W, et al. A molecular mechanics/grid method for evaluation of ligand-receptor interactions [J]. Journal of Computational Chemistry, 1995, 16, 454-464.
[148]唐敖庆.量子化学[M].北京:科学出版社, 1982
[149]唐敖庆,杨忠志.大分子体系的量子化学[M].长春:吉林大学出版社,2000.
[150]田安民.量子化学[M].四川:四川大学出版社,1989.
[151]廖沐真.量子化学从头计算方法[M].北京:清华大学出版社,1989.
[152]江逢霖.量子化学原理[M].上海:复旦大学出版社,1990.
[153] SLATER J C. Quantum Theory of Molecular and Solids. Vol. 4: The Self-Consistent Field for Molecular and Solids McGraw-Hill: New York, 1974.
[154] SALAHUB D R, ZERNER M C. The Challenge of d and f Electrons ACS: Washington, D.C. 1989
[155] PARR R G, YANG W. Density-functional theory of atoms and molecules Oxford Univ. Press: Oxford, 1989
[156] WRIGHT J R. Immunoregulatory functions of surfactant proteins [J]. Nature Reviews Immunology, 2005, 5: 58-68.
[157] ERPENBECK V J, KRUG N, HOHLFELD J M. Therapeutic use of surfactant components in allergic asthma [J]. Naunyn-Schmiedeberg’s Archives of Pharmacology, 2009, 379: 217-224.
[158] KINGMA P S, WHITSETT J A. In defense of the lung: surfactant protein A and surfactant protein D [J]. Current Opinion in Pharmacology, 2006, 6: 277-283.
[159] VIGERUST D J, SHEPHERD V L. Virus glycosylation: role in virulence and immune interactions [J]. TRENDS in Microbiology, 2007, 15: 211-218.
[160] GUPTA G, SUROLIA A. Collectins: sentinels of innate immunity [J]. Bioessays, 2007, 29: 452-464.
[161] KISHORE U, GREENHOUGH T J, WATERS P, SHRIVE A K, GHAI R, KAMRAN M F, BERNAL A L, REID K B M, MADAN T, CHAKRABORTY T. Surfactant protein SP-A and SP-D: Structure, function and receptors [J]. Molecular Immunology, 2006, 43: 1293-1315.
[162] PASTVA A M, WRIGHT J R, WILLIAMS K L. Immunomodulatory Roles of Surfactant Proteins A and D: Implications in Lung Disease [J]. Preceedings of the American Thoracic Society, 2007, 4: 252-257.
[163] HACZKU A. Protective role of the lung collectins surfactant protein A and surfactant protein D in airway inflammation [J]. Journal of Allergy and Clinical Immunology, 2008, 122: 861-879.
[164] DAHL M. Biomarkers for Chronic Obstructive Pulmonary Disease: Surfactant Protein D and C-Reactive Protein [J]. American Journal of Respiratory and Critical Care Medicine, 2008, 177: 1177-1178.
[165] HARTSHORN K L, CROUCH E C, WHITE M R, EGGLETON P, TAUBER A I, CHANG D, SASTRY K. Evidence for a Protective Role of Pulmonary Surfactant Protein D (SP-D) against Influenza A Viruses [J]. Journal of Clinical Investigation, 1994, 94: 311-319.
[166] HARTSHORN K L, WEBBY R, WHITE M R, TECLE T, PAN C, BOUCHER S, MORELAND R J, CROUCH E C, SCHEULE R K. Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D [J]. Respiratory Research, 2008, 9: 65-76.
[167] CROUCH E, HARTSHORN K, HORLACHER T, MCDONALD B, SMITH K, CAFARELLA T, SEATON B, SEEBERGER P H, HEAD J. Recognition of Mannosylated Ligands and Influenza A Virus by Human Surfactant Protein D: Contributions of an Extended Site and Residue 343 [J]. Biochemistry, 2009, 48: 3335-3345.
[168] MESCHI J, CROUCH E C, SKOLNIK P, YAHYA K, HOLMSKOV U, LETH-LARSEN R, TORNOE I, TECLE T, WHITE M R, HARTSHORN K L. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication [J]. Journal of General Virology, 2005, 86: 3097-3107.
[169] HOLMSKOV U L. Collectins and collectin receptors in innate immunity [J]. APMIS Suppl, 2000, 100: 1-59.
[170] KUROKI Y, VOELKER D R. Pulmonary Surfactant Proteins [J]. Journal ofBiological Chemistry, 1994, 269: 25943-25946.
[171] PERSSON A, CHANG D, CROUCH E. Surfactant Protein D Is a Divalent Cation-dependent Carbohydrate-binding Protein [J]. Journal of Biological Chemistry, 1990, 265: 5755-5760.
[172] CROUCH E, MCDONALD B, SMITH K, ROBERTS M, MEALY T, SEATON B, HEAD J. Critical Role of Arg/Lys343 in the Species-Dependent Recognition of Phosphatidylinositol by Pulmonary Surfactant Protein D [J]. Biochemistry, 2007, 46: 5160-5169.
[173] NIE X, NISHITANI C, YAMAZOE M, ARIKI S, TAKAHASHI M, SHIMIZU T, MITSUZAWA H, SAWADA K, SMITH K, CROUCH E, NAGAE H, TAKAHASHI H, KUROKI Y. Pulmonary Surfactant Protein D Binds MD-2 through the Carbohydrate Recognition Domain [J]. Biochemistry, 2008, 47: 12878-12885.
[174] SHRIVE A K, THARIA H A, STRONG P, KISHORE U, BURNS I, RIZKALLAH P J, REID K B M, GREENHOUGH T J. High-resolution Structural Insights into Ligand binding and Immune Cell Recognition by Human Lung Surfactant Protein D [J]. Journal of Biological Chemistry, 2003, 331: 509-523.
[175] CROUCH E C, SMITH K, MCDONALD B, BRINER D, LINDERS B, MCDONALD J, HOLMSKOV U, HEAD J, HARTSHORN K. Species Differences in the Carbohydrate Binding Preferences of Surfactant Protein D [J]. American Journal of Respiratory Cell and Molecular Biology, 2006, 35: 84-94.
[176] PERSSON A V, GIBBONS B J, SHOEMAKER J D, MOXLEY M A, LONGMORE W J. The Major Glycolipid Recognized by SP-D in Surfactant Is Phosphatidylinositol [J]. Biochemistry, 1992, 31: 12183-12189.
[177] OGASAWARA Y, KUROKI Y, AKINO T. Pulmonary Surfactant Protein D Specifically Binds to Phosphatidylinositol [J]. Journal of Biological Chemistry, 1992, 267: 21244-21249.
[178] LU J, WILLIS A C, REID K B M. Purification, characterization and cDNA cloning of human lung surfactant protein D [J]. Biochemical Journal, 1992, 284:795-802.
[179] THORMANN E, DREYER J K, SIMONSEN A C, HANSEN P L, HANSEN S, HOLMSKOV U, MOURITSEN O G. Dynamic Strength of the Interaction between Lung Surfactant Protein D (SP-D) and Saccharide Ligands [J]. Biochemistry, 2007, 46: 12231-12237.
[180] Discovery Studio 2.1, San Diego: Accelrys, CA 92121, USA, 2008.
[181] WU G, ROBERTSON D H, BROOKS III C L, VIETH M. Detailed Analysis of Grid-Based Molecular Docking: A Case Study of CDOCKER—A CHARMm-Based MD Docking Algorithm [J]. Journal of Computational Chemistry, 2003, 24: 1549-1562.
[182] PHILLIPS J C, BRAUN R, WANG W, GUMBART J, TAJKHORSHID E, VILLA E, CHIPOT C, SKEEL R D, KALéL, SCHULTEN K. Scalable Molecular Dynamics with NAMD [J]. Journal of Computational Chemistry, 2005, 26: 1781-1802.
[183][29] GUVENCH O, GREENE S N, KAMATH G, BRADY J W, VENABLE R M, PASTOR R W, MACKERELL A D, JR. Additive Empirical Force Field for Hexopyranose Monosaccharides [J]. Journal of Computational Chemistry, 2008, 29: 2543-2564.
[184] HUMPHREY W, DALKE A, SCHULTEN K. VMD: Visual Molecular Dynamics [J]. Journal of Molecular Graphics, 1996, 14: 33-38.
[185] JORGENSEN W L, CHANDRASEKHAR J, MADURA J D, IMPEY R W, KLEIN M L. Comparison of simple potential functions for simulating liquid water [J]. Journal of Chemical Physics, 1983, 79: 926-935.
[186] DARDEN T, YORK D, PEDERSEN L. Particle mesh Ewald: An N?log(N) method for Ewald sums in large systems [J]. Journal of Chemical Physics, 1993, 98: 10089-10092.
[187] TOUKMAJI A Y, BOARD J J A. Ewald summation techniques in perspective: a survey [J]. Computer Physics Communications, 1996, 95: 73-92.
[188] FELLER S E, ZHANG Y, PASTOR R W. Constant pressure molecular dynamics simulation: The Langevin piston method [J]. Journal of ChemicalPhysics, 1995, 103: 4613-4621.
[189] LU H, ISRALEWITZ B, KRAMMER A, VOGEL V, SCHULTEN K. Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation [J]. Biophysical Journal, 1998, 75(2): 662-671.
[190] ZHANG Q, LU Z, HU H, YANG W, MARSZALEK P E. Direct Detection of the Formation of V-Amylose Helix by Single Molecule Force Spectroscopy [J]. Journal of the American Chemical Society, 2006, 128(29): 9387-9393.
[191] ZHANG D, GULLINGSRUD J, MCCAMMON J A. Potentials of Mean Force for Acetylcholine Unbinding from the Alpha7 Nicotinic Acetylcholine Receptor Ligand-Binding Domain [J]. Journal of the American Chemical Society, 2006, 128(9): 3019-3026.
[192] LIU X, XU Y, WANG X, BARRANTES F J, JIANG H. Unbinding of Nicotine from the Acetylcholine Binding Protein: Steered Molecular Dynamics Simulations [J]. Journal of Physical Chemistry B, 2008, 112(13):4087-4093.
[193] DARVE E, POHORILLE A. Calculating free energies using average force [J]. Journal of Chemical Physics, 2001, 115: 9169-9183.
[194] DEN OTTER W K. Thermodynamic integration of the free energy along a reaction coordinate in Cartesian coordinates [J]. Journal of Chemical Physics, 2000, 112: 7283-7292.
[195] HéNIN J, CHIPOT C. Overcoming free energy barriers using unconstrained molecular dynamics simulations [J]. Journal of Chemical Physics, 2004, 121: 2904-2914.
[196] BARTELS C, KARPLUS M. Multidimensional adaptive umbrella sampling: Applications to main chain and side chain peptide conformations [J]. Journal of Computational Chemistry, 1997, 18(12): 1450-1462.
[197] BARTELS C, KARPLUS M. Probability Distributions for Complex Systems: Adaptive Umbrella Sampling of the Potential Energy [J]. Journal of Physical Chemistry B, 1998, 102(5): 865-880.
[198] RODRIGUEZ-GOMEZ D, DARVE E, POHORILLE A. Assessing the efficiency of free energy calculation methods [J]. Journal of Chemical Physics,2004, 120(8): 3563-3578.
[199] IZRAILEV S, STEPANIANTS S, BALSERA M, OONO Y, SCHULTEN K. Molecular dynamics study of unbinding of the avidin-biotin complex [J]. Biophysical Journal, 1997, 72(4): 1568-1581.
[200] ISRALEWITZ B, IZRAILEV S, SCHULTEN K. Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulations [J]. Biophysical Journal, 1997, 73(6): 2972-2979.
[201] KOSZTIN D, IZRAILEV S, SCHULTEN K. Unbinding of Retinoic Acid from its Receptor Studied by Steered Molecular Dynamics [J]. Biophysical Journal, 1999, 76(1): 188-197.
[202] GRUBMüLLER H, HEYMANN B, TAVAN P. Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force [J]. Science, 1996, 271: 997-999.
[203] SEBOLT-LEOPOLD J S, HERRERA R. Targeting the mitogen-activated protein kinase cascade to treat cancer [J]. Nature Reviews Cancer, 2004, 4(12): 937-947.
[204] SMALLEY K S M. A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? [J]. International Journal of Cancer, 2003, 104(5): 527-532.
[205] KOHNO M, POUYSSEGUR J. Targeting the ERK signaling pathway in cancer therapy [J]. Annals of Medicine, 2006, 38(3): 200-211.
[206] HILGER R A, SCHEULEN M E, STRUMBERG D. The Ras-Raf-MEK-ERK pathway in the treatment of cancer [J]. Onkologie, 2002, 25(6): 511-518.
[207] LEFLOCH R, POUYSSEGUR J, LENORMAND P. Total ERK1/2 activity regulates cell proliferation [J]. Cell Cycle, 2009, 8(5):705-711.
[208] CHAMBARD J C, LEFLOCH R, POUYSSEGUR J, LENORMAND P. ERK implication in cell cycle regulation [J]. Biochimica et Biophysica Acta-Molecular Cell Research, 2007, 1773(8):1299-1310.
[209] HERRERA R, SEBOLT-LEOPOLD J S. Unraveling the complexities of the Raf/MAP kinase pathway for pharmacological intervention [J]. Trends inMolecular Medicine, 2002, 8(4): S27-S31.
[210] KYRIAKIS J M, AVRUCH J. Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation [J]. Physiological Reviews, 2001, 81(2): 807-869.
[211] HO A K, HASHIMOTO K, CHIK C L. 3',5'-Cyclic Guanosine Monophosphate Activates Mitogen-Activated Protein Kinase in Rat Pinealocytes [J]. Journal of Neurochemistry, 1999, 73(2):598-604.
[212] LEFLOCH R, POUYSSEGUR J, LENORMAND P. Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels [J]. Molecular and Cellular Biology, 2008, 28(1): 511-527.
[213] ARONOV A M, BAKER C, BEMIS G W, CAO J R, CHEN G J, FORD P J, GERMANN U A, GREEN J, HALE M R, JACOBS M, JANETKA J W, MALTAIS F, MARTINEZ-BOTELLA G, NAMCHUK M N, STRAUB J, TANG Q, XIE X L. Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors [J]. Journal of Medicinal Chemistry, 2007, 50(6):1280-1287.
[214] HU G D, ZHANG S L, ZHANG Q G. Molecular Dynamics Simulations and Free Energy Calculation of FKBP12 Protein and Its Inhibitors [J]. Acta Chimica Sinica, 2009, 67(9): 1019-1025.
[215] MA G Z, LIU C, QIU Y F, NAN J M. Minor Groove Binding between DB818 and DNA: a Molecular Dynamics Simulation and Binding Free Energy Analysis [J]. Acta Chimica Sinica, 2009, 67(5): 453-458.
[216] DE GROOT C O, JELESAROV I, DAMBERGER F F, BJELIC S, SCHARER M A, BHAVESH N S, GRIGORIEV I, BUEY R M, WUTHRICH K, CAPITANI G, AKHMANOVA A, STEINMETZ M O. Molecular Insights into Mammalian End-binding Protein Heterodimerization [J]. Journal of Biological Chemistry, 2010, 285(8): 5802-5814.
[217] DAL BEN D, ANTONINI I, BUCCIONI M, LAMBERTUCCI C, MARUCCI G, VITTORI S, VOLPINI R, CRISTALLI G. Molecular Modeling Studies on theHuman Neuropeptide S Receptor and Its Antagonists [J]. ChemMedChem, 2010, 5(3): 371-383.
[218] BHUIYAN M A, ISHIGURO M, HOSSAIN M, NAKAMURA T, OZAKI M, MIURA S, NAGATOMO T. Binding sites of valsartan, candesartan and Iosartan with angiotensin II receptor 1 subtype by molecular modeling [J]. Life Sciences, 2009, 85(3-4): 136-140.
[219] Insight II, Molecular Simulation Inc. San Diego, 2000.
[220] MORRIS A L, MACARTHUR M W, HUTCHINSON E G, THORNTON J M. Stereochemical quality of protein structure coordinates [J]. Proteins, 1992, 12(4): 345-364.
[221] FOLOPPE N, FISHER L M, HOWES R, KIERSTAN P, POTTER A, ROBERTSON A G S, SURGENOR A E. Structure-based design of novel Chk1 inhibitors: Insights into hydrogen bonding and protein-ligand affinity [J]. Journal of Medicinal Chemistry, 2005, 48(18): 4332-4345.
[222] KRISHNAMURTHY V M, KAUFMAN G K, URBACH A R, GITLIN I, GUDIKSEN K L, WEIBEL D B, WHITESIDES G M. Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein?Ligand Binding [J]. Chemical Reviews, 2008, 108(3): 946-1051.
[223] SCOZZAFAVA A, MASTROLORENZO A, SUPURAN C T. Carbonic anhydrase inhibitors and activators and their use in therapy [J]. Expert Opinion On Therapeutic Patents, 2006, 16(12):1627-1664.
[224] PASTOREKOVA S, PARKKILA S, PASTOREK J, SUPURAN C T. Carbonic anhydrases: Current state of the art, therapeutic applications and future prospects [J]. Journal of Enzyme Inhibition and Medicinal Chemistry, 2004, 19(3):199-229.
[225] SUPURAN C T, SCOZZAFAVA A. Applications of carbonic anhydrase inhibitors and activators in therapy [J]. Expert Opinion On Therapeutic Patents, 2002, 12(2): 217-242.
[226] SUPURAN C T, CASINI A, SCOZZAFAVA A. Protease inhibitors of the sulfonamide type: Anticancer, antiinflammatory, and antiviral agents [J].Medicinal Research Reviews, 2003, 23(5): 535-558.
[227] SCHUMAN J S. Short- and long-term safety of glaucoma drugs [J]. Expert Opin Drug Saf, 2002, 1(2): 181-194.
[228] SUPURAN C T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators [J]. Nature Reviews Drug Discovery, 2008, 7(2): 168-181.
[229] WINUM J Y, RAMI M, SCOZZAFAVA A, MONTERO J L, SUPURAN C. Carbonic anhydrase IX: A new druggable target for the design of antitumor agents [J]. Medicinal Research Reviews, 2008, 28(3): 445-463.
[230] DI FIORE A, MONTI S M, HILVO M, PARKKILA S, ROMANO V, SCALONI A, PEDONE C, SCOZZAFAVA A, SUPURAN C T, DE SIMONE G. Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide [J]. Proteins-Structure Function and Bioinformatics, 2009, 74(1):164-175.
[231] KHALIFAH R G. The Carbon Dioxide Hydration Activity of Carbonic Anhydrase: I. STOP-FLOW KINETIC STUDIES ON THE NATIVE HUMAN ISOENZYMES B AND C [J]. Journal of Biological Chemistry, 1971, 246: 2561-2573.
[232] ELDER I, FISHER Z, LAIPIS P J, TU C, MCKENNA R, SILVERMAN D N. Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III [J]. Proteins-Structure Function and Bioinformatics, 2007, 68(1): 337-343.
[233] HILVO M, BARANAUSKIENE L, SALZANO A M, SCALONI A, MATULIS D, INNOCENTI A, SCOZZAFAVA A, MONTI S M, DI FIORE A, DE SIMONE G, LINDFORS M, JANIS J, VALJAKKA J, PASTOREKOVA S, PASTOREK J, KULOMAA M S, NORDLUND H R, SUPURAN C T, PARKKILA S. Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes [J]. Journal of Biological Chemistry, 2008, 283(41): 27799-27809.
[234] MONTGOMERY J C, VENTA P J, EDDY R L, FUKUSHIMA Y S, SHOWS TB, TASHIAN R E. Characterization of the human gene for a newly discovered carbonic anhydrase, CA VII, and its localization to chromosome 16 [J]. Genomics, 1991, 11(4): 835-848.
[235] HALMI P, PARKKILA S, HONKANIEMI J. Expression of carbonic anhydrases II, IV, VII, VIII and XII in rat brain after kainic acid induced status epilepticus [J]. Neurochemistry International, 2006, 48(1):24-30.
[236] RUUSUVUORI E, LI H, HUTTU K, PALVA JM, SMIRNOV S, RIVERA C, KAILA K, VOIPIO J. Carbonic anhydrase isoform VII acts as a molecular switch in the development of synchronous gamma-frequency firing of hippocampal CA1 pyramidal cells [J]. Journal of Neuroscience, 2004, 24(11):2699-2707.
[237] RIVERA C, VOIPIO J, KAILA K. Two developmental switches in GABAergic signalling: the K+-Cl- cotransporter KCC2 and carbonic anhydrase CAVII [J]. Journal of Physiology-London, 2005, 562(1): 27-36.
[238] GüZEL ?, INNOCENTI A, SCOZZAFAVA A, SALMAN A, SUPURAN CT. Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors [J]. Bioorganic & Medicinal Chemistry Letters, 2009, 19(12): 3170-3173.
[239] Insight II User Guide, San Diego:Biosym/MSI (2000)
[240] SAAM J, IVANOV I, WALTHER M, HOLZHUETTER H G, KUHN H. Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels [J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(33):13319-13324.
[241] Gaussian 03, Revision E.01 [M], Gaussian, Inc., Pittsburgh PA, (2003).
[242] Insight II Homology User Guide, San Diego: Accelrys Inc (2000).
[243] ALTSCHUL S F, MADDEN T L, SCHAFFER A A, ZHANG J, ZHANG Z, MILLER W, LIPMAN D J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J]. Nucleic Acids Res, 1997, 25(17):3389-3402.
[244] SALI A, OVERINGTON J P. Derivation of rules for comparative protein modeling from a database of protein structure alignments [J]. Protein Sci, 1994, 3(9): 1582-1596.
[245] SALI A, POTTERTON L, YUAN F, VAN VLIJMEN H, KARPLUS M. Evaluation of comparative protein modeling by MODELLER [J]. Proteins, 1995, 23(3): 318-326.
[246] SALI A. Modeling mutations and homologous proteins [J]. Current Opinion in Biotechnology, 1995, 6(4):437-451.
[247] Insight II Profile-3D User Guide, San Diego: Biosym/MSI (2000).
[248] LASKOWSKI R A, MOSS D S, THORNTON J M. Main-chain bond lengths and bond angles in protein structures [J]. Journal of Molecular Biology, 1993, 231(4): 1049-1067.
[249] KOLLMAN P A, MASSOVA I, REYES C, KUHN B, HUO S H, CHONG L, LEE M, LEE T, DUAN Y, WANG W, DONINI O, CIEPLAK P, SRINIVASAN J, CASE D A, CHEATHAM T E. Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models [J]. Accounts of Chemical Research, 2000, 33(12): 889-897.
[250] HüNENBERGER PH, HELMS V, NARAYANA N, TAYLOR SS, MCCAMMON JA. Determinants of Ligand Binding to cAMP-Dependent Protein Kinase [J]. Biochemistry, 1999, 38(8): 2358-2366.
[251] SIROCKIN F, SICH C, IMPROTA S, SCHAEFER M, SAUDEK V, FROLOFF N, KARPLUS M, DEJAEGERE A. Structure Activity Relationship by NMR and by Computer: A Comparative Study [J] Journal of the American Chemical Society, 2002, 124(37): 11073-11084.
[252] KREBS H A. Inhibition of carbonic anhydrase by sulphonamides [J]. Biochemical Journal, 1948, 43: 525-528.
[253] DUDA D, GOVINDASAMY L, AGBANDJE-MCKENNA M, TU C, SILVERMAN DN, MCKENNA R. The refined atomic structure of carbonic anhydrase II at 1.05 angstrom resolution: implications of chemical rescue of proton transfer [J]. Acta Crystallographica Section D-BiologicalCrystallography, 2003, 59(1):93-104.
[254] VULLO D, INNOCENTI A, NISHIMORI I, PASTOREK J, SCOZZAFAVA A, PASTOREKOVáS, SUPURAN C T. Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides - a new target for the design of antitumor and antiglaucoma drugs? [J]. Bioorganic & Medicinal Chemistry Letters, 2005, 15(4):971-976.
[255] BORIACK-SJODIN P A, ZEITLIN S, CHEN H H, CRENSHAW L, GROSS S, DANTANARAYANA A, DELGADO P, MAY JA, DEAN T, CHRISTIANSON DW. Structural analysis of inhibitor binding to human carbonic anhydrase II [J]. Protein Science, 1998, 7: 2483-2489.
[2]张春霆.生物信息学的现状与展望[J].世界科技研究与发展, 2000, 22(6):17-20.
[3]王正华,王勇献.后基因组时代生物信息学的新进展[J].国防科技大学学报,2003, 25(1):1-6.
[4] CALIFANO A. Advances in Sequence Analysis [J]. Current Opinion in Structural Biology, 2002, 11(3):330-333.
[5] KUNDU A, BAYYA A. Speech Recognition Using Bybrid Hidden Markov Model and NN Classifier [J]. International Journal of Speech Technology, 1998, 2(3):227-240.
[6]郑珂晖.生物信息学的背景、现状及前景[J].农业网络信息, 2005, (2):4-7.
[7]陈润生.生物信息学及其研究进展[J].医学研究通讯, 2002, 31(12):2-5.
[8]王发生,毛君莲.生命科学时代的生物信息学[J].中国现代医学杂志, 2000, 10(12):108-109.
[9]赵南明,周海梦,等.生物物理学[M].北京:高等教育出版社,2000.
[10] CHUNG V, WAKEFIELD A E, KINSMAN O S, et al. DNA amplification of a portion of the phosphomannose isomerase (PMI) gene in Pneumocystis carinii-enriched extracts [J]. Journal of Eukaryotic Microbiology, 1994, 41:82S-83S.
[11] MCCAMMON J A, GELIN B R, KARPLUS M. Dynamics of folded proteins [J]. Nature, 1977, 267:585-590.
[12] WELLS T N, PAYTON M A, PROUDFOOT A E. Inhibition of phosphomannose isomerase by mercury ions [J]. Biochemistry, 1994, 33:7641-7646.
[13] GONEN T, CHENG Y, SLIZ P, et al. Lipid-protein interactions in double-layered two-dimensional AQP0 crystals [J]. Nature, 2005, 438:633-638.
[14] WELLS T N, SCULLY P, MAGNENAT E. Arginine 304 is an active site residue in phosphomannose isomerase from Candida albicans [J]. Biochemistry, 1994,
[44] BEN-TAL N, SITKOFF D, BRANSBURG-ZABARY S, et al. Theoretical calculations of the permeability of monensin-cation complexes in model bio-membranes [J]. Biochimica et biophysica acta, 2000, 1466: 221-233.
[45] SIVOZHELEZOV V, NICOLINI C, KARPINSKI S, et al. Toward a blueprint for UDP-glucose pyrophosphorylase structure/function properties: homology-modeling analyses [J]. Plant Molecular Biology, 2004, 56:783-794.
[46] LEE K W, BRIGGS J M. Molecular modeling study of the editing active site of Escherichia coli leucyl-tRNA synthetase: two amino acid binding sites in the editing domain [J]. Proteins, 2004, 54:693-704.
[47] ROY S, SEN S. Homology Modeling Based Solution Structure of Hoxc8-DNA Complex: Role of Context Bases Outside TAAT Stretch [J]. Journal of Biomolecular Structure & Dynamics, 2005, 22: 707-718.
[48] ROHL C A, STRAUSS C E, CHIVIAN D, et al. Modeling structurally variable regions in homologous proteins with rosetta [J]. Proteins, 2004, 55: 656-677.
[49] Chothia C. One thousand families for the molecular biologist [J]. Nature, 1992, 357:543-544.
[50] Wang Z X. A re-estimation for the total numbers of protein folds and superfamilies [J]. Protein Engineering, 1998, 11(8):621-626.
[51] THOMAS P D, DILL K A. An iterative method for extracting energy-like quantities from protein structures [J]. Proceedings of the National Academy of Sciences of the United States of America, 1996, 93(21):11628-11633.
[52] LATHROP R H, SMITH T F. Global optimum protein threading with gapped alignment and empirical pair score functions [J]. Journal of Molecular Biology, 1996, 255(4):641-665.
[53] FISCHER D, EISENBERG D. Protein fold recognition using sequence-derived predictions [J]. Protein Science, 1996, 5(5):947-955.
[54] STERNBERG M J, BATES P A, KELLEY L A, MACCALLUM R M. Progress in protein structure prediction: assessment of CASP3 [J]. Current Opinion in Structural Biology, 1999, 9(3):368-373.
[55] HOLLAND J H. Adaptation in Natural and Artificial Systems [M]. Ann Arbor,Boston: The University of Michigan Press, 1975.
[56]解伟,王翼飞.蛋白质折叠的三维计算机模拟[J].上海大学学报(自然科学版), 2000, 6(2):145-149.
[57] B?HM H J, KLEBE G. What can we learn from molecular recognition in protein-ligand complexes for the design of new drugs? [J]. Angew Chem Int Ed Engl, 1996, 35(22):2588-2614.
[58]张阳德.生物信息学(5):药物设计与生物信息学[J].外科理论与实践, 2007, 12(2):附41-附47.
[59]陈凯先.计算机辅助药物设计:原理、方法及应用[M].上海:上海科学技术出版社, 2000.
[60]李亮助,孙强明.生物信息学在药物设计中的应用[J].生命的化学, 2003, 23(5):364-366.
[61]郑彦,吕莉.计算机辅助药物设计在药物合成中的应用[J].齐鲁药事, 2008, 27(10):614-616.
[62]赵金城,王庆莉,毕秀玲.计算机辅助直接药物分子设计[J].大连大学学报,2002, 23(6):22-30.
[63] B?HM H J. LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads [J]. J Comput Aided Mol Des, 1992, 6(1):593-606.
[64] STERNBERG M J E. Protein structure prediction-a piratical approach Oxford: Oxford Press, 1996.
[65] BLUNDELL T L, CARNEY D, GARDNER S, et al. Knowledge-based protein modelling and design [J]. European Journal of Biochemistry, 1988, 172:513-520.
[66] SANCHEZ R, SALI A. Comparative protein structure modeling in genomics [J]. Journal of Computational Physics, 1999, 151(1): 388-401.
[67] SALI A, OVERINGTON J P, JOHNSON M S, et al. From comparisons of protein sequences and structures to protein modeling and design [J]. Trends in Biochemical Sciences, 1990, 15(6): 235-240.
[68] BLUNDELL T L, SIBANDA B L, STERNBERG M J E, et al. Knowledge-based prediction of protein structures and the design of novel molecules [J]. Nature, 1987, 326: 347-352.
[69]张漫,常延琦.蛋白质三级结构预测方法简述[J].中国动物检疫, 2005, 22(5):36-37.
[70]来鲁华等.蛋白质的结构预测与分子设计[M].北京大学出版社, 1993.
[71] NEEDLEMAN S B, WUNSCH C D. A general method applicable to search for similarities in the amino acid sequence of two proteins [J]. Journal of Molecular Biology, 1970, 48(3): 443-453.
[72] SMITH T F, WATERMAN M S. Identification of common molecular subsequences [J]. Journal of Molecular Biology, 1981, 147(1):195-197.
[73] LIPMAN D J, PEARSON W R. Rapid and sensitive protein similarity searches [J]. Science, 1985, 227:1435-1441.
[74] PEARSON W R, LIPMAN D J. Improved tools for biological sequence comparison [J]. Proc Natl Acad Sci USA, 1988, 85(8):2444-2448.
[75] ALTSCHUL S F, GISH W, MILLER W, MYERS E W, LIPMAN D J. Basic local alignment search tool [J]. Journal of Molecular Biology, 1990, 215(3):403-410.
[76] ALTSCHUL S F, GISH W. Local alignment statistics [J]. Methods Enzymol, 1996, 266:460-480.
[77] FENG D, DOOLITTLE R F. Progressive sequence alignment as a pre-requisite to correct phylogenetic trees [J]. J Mol Evol, 1987, 60:351-360.
[78] ANDREW R L. Molecular Modeling: Principles and Applications, 1996, Addison Wesley Longman Limited, London
[79] KAO J, ALLINGER N L. Conformational analysis. 122. Heats of formation of conjugated hydrocarbons by the force field method [J]. Journal of the American Chemical Society, 1977, 99(4): 975-986.
[80] ALLINGER N L, YAN L Q. Molecular mechanics (MM3). Calculations of furan, vinyl ethers, and related compounds [J]. Journal of the American Chemical Society, 1993, 115(25):11918-11925.
[81] ALLINGER N L, CHEN K, LII J H. An improved force field (MM4) for saturated hydrocarbons [J]. Journal of Computational Chemistry, 1996, 17(5):642-668.
[82] NEVINS N, CHEN K, ALLINGER N L. Molecular mechanics (MM4)calculations on alkenes [J]. Journal of Computational Chemistry, 1996, 17(5):669-694.
[83] HALGREN T A. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 [J]. Journal of Computational Chemistry, 1996, 17(5):490-519.
[84] HALGREN T A, NACHBAR R B. Merck molecular force field. IV. conformational energies and geometries for MMFF94 [J]. Journal of Computational Chemistry, 1996, 17(5):587-615.
[85] WEINER S J, KOLLMAN P A, NGUYEN D T, CASE D A. An all atom force field for simulations of proteins and nucleic acids [J]. Journal of Computational Chemistry, 1986, 7(2): 230-252.
[86] WEINER S J, KOLLMAN P A, CASE D A, SINGH U C, GHIO C, ALAGONA G, PROFETA S, WEINER P. A new force field for molecular mechanical simulation of nucleic acids and proteins [J]. Journal of the American Chemical Society, 1984, 106(3):765-784.
[87] CORNELL W D, CIEPLAK P, BAYLY C I, GOULD I R, MERZ K M, FERGUSON D M, SPELLMEYER D C, FOX T, CALDWELL J W, KOLLMAN P A. A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules [J]. Journal of the American Chemical Society, 1995, 117(19):5179-5197.
[88] BROOKS B R, BRUCCOLERI R E, OLAFSON B D, STATES D J, SWAMINATHAN S, KARPLUS M. CHARMM: A program for macromolecular energy, minimization, and dynamics calculations [J]. Journal of Computational Chemistry, 1983, 4(2): 187-217.
[89] MOMANY F A, RONE R. Validation of the general purpose QUANTA ?3.2/CHARMm? force field [J]. Journal of Computational Chemisty, 1992, 13: 888-900.
[90] MACKERELL A D, JR, WIORKIEWICZ-KUCZERA J, KARPLUS M. An all-atom empirical energy function for the simulation of nucleic acids [J]. Journal of the American Chemical Society, 1995, 117(48):11946-11975.
[91] MACKERELL A D, JR, BASHFORD D, BELLOTT M, et al. All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins [J] Journal of Physical Chemistry B, 1998, 102(18):3586-3616.
[92] HAGLER A T, HULER E, LIFSON S. Energy functions for peptides and proteins. I. Derivation of a consistent force field including the hydrogen bond from amide crystals [J]. Journal of the American Chemical Society, 1974, 96(17): 5319-5327.
[93] HAGLER A T, LIFSON S. Energy functions for peptides and proteins. II. Amide hydrogen bond and calculation of amide crystal properties [J]. Journal of the American Chemical Society, 1974, 96(17): 5327-5335.
[94] LIFSON S, HAGLER A T, DAUBER P. Consistent force field studies of intermolecular forces in hydrogen-bonded crystals. 1. Carboxylic acids, amides, and the C:O.cntdot..cntdot..cntdot.H- hydrogen bonds [J] Journal of the American Chemical Society, 1979, 101(18): 5111-5121.
[95] HAGLER A T, LIFSON S, DAUBER P. Consistent force field studies of intermolecular forces in hydrogen-bonded crystals. 2. A benchmark for the objective comparison of alternative force fields [J] Journal of the American Chemical Society, 1979, 101(18): 5122-5130.
[96] HAGLER A T, DAUBER P, LIFSON S. Consistent force field studies of intermolecular forces in hydrogen-bonded crystals. 3. The C:O.cntdot..cntdot..cntdot.H-O hydrogen bond and the analysis of the energetics and packing of carboxylic acids [J]. Journal of the American Chemical Society, 1979, 101(18): 5131-5141.
[97] KITSON D H, HAGLER A T. Theoretical studies of the structure and molecular dynamics of a peptide crystal [J] Biochemistry, 1988, 27(14):5246-5257.
[98] KITSON D H, HAGLER A T. Catalysis of a rotational transition in a peptide by crystal forces [J]. Biochemistry, 1988, 27(19): 7176-7180.
[99] DAUBER-OSGUTHORPE P, ROBERTS V A, OSGUTHORPE D J, WOLFF J, GENEST M, HAGLER A T. Structure and energetics of ligand binding to proteins: Escherichia coli dihydrofolate reductase-trimethoprim, a drug-receptor system [J] Proteins: Structure, Function, and Genetics, 1988, 4(1):31-47.
[100] MAPLE J R, HWANG M J, STOCKFISCH T P, DINUR U, WALDMAN M, EWIG C S, HAGLER A T. Derivation of class II force fields. I. Methodology and quantum force field for the alkyl functional group and alkane molecules [J] Journal of Computational Chemistry, 1994, 15(2):162-182.
[101] MAPLE J R, DINUR U, HAGLER A T. Derivation of force fields for molecular mechanics and dynamics from ab initio energy surfaces [J]. Proc. Nat. Acad. Sci. USA, 1988, 85(15):5350-5354.
[102] HWANG M J, STOCKFISCH T P, HAGLER A T. Derivation of Class II Force Fields. 2. Derivation and Characterization of a Class II Force Field, CFF93, for the Alkyl Functional Group and Alkane Molecules [J]. Journal of the American Chemical Society, 1994, 116(6): 2515-2525.
[103] MAPLE J R, HWANG M J, JALKANEN K J, STOCKFISCH T P, HAGLER A T. Derivation of class II force fields: V. Quantum force field for amides, peptides, and related compounds [J]. Journal of Computational Chemistry, 1998, 19(4):430-458.
[104] SUN H, MUMBY S J, MAPLE J R, HAGLER A T. An ab Initio CFF93 All-Atom Force Field for Polycarbonates [J]. Journal of the American Chemical Society, 1994, 116(7): 2978-2987.
[105] SUN H, MUMBY S J, MAPLE J R, HAGLER A T. Ab Initio Calculations on Small Molecule Analogs of Polycarbonates [J]. Journal of Physical Chemistry, 1995, 99(16): 5873-5882.
[106] SUN H. Ab initio calculations and force field development for computer simulation of polysilanes [J]. Macromolecules, 1995, 28(3):701-712.
[107] SUN H. Ab initio characterizations of molecular structures, conformation energies, and hydrogen-bonding properties for polyurethane hard segments [J]. Macromolecules, 1993, 26(22):5924-5936.
[108] PAPPE A K, CASEWIT C J, COLWELL K S, et al. UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations [J]. Journal of the American Chemical Society, 1992, 114 : 10024-10035.
[109] MAYO S L, OLAFSON B D, GODDARD W A. DREIDING: A Generic ForceField for Molecular Simulations [J]. Journal of Physical Chemistry, 1990, 94: 8897-8909.
[110] BUNTE S W. Molecular Modeling of Energetic Materials: The Parameterization and Validation of Nitrate Esters in the COMPASS Force Field [J]. Journal of Physical Chemistry B, 2001, 104, 2477-2489.
[111] CASEWIT C J, COLWELL K S, RAPPE A K. Application of a universal force field to organic molecules [J]. Journal of the American Chemical Society, 1992, 114, 10035-10046.
[112] ROSENTHAL A B, GAROFALINI S H. Molecular dynamics of amorphous titanium silicate [J]. Journal of Non-Crystalline Solids, 1988, 107, 65-72.
[113] KOHLER A E, GAROFALINI S H. Effect of Composition on the Penetration of Inert Gases Adsorbed onto Silicate Glass Surfaces [J]. Langmuir, 1994, 10, 4664-4669.
[114] LEVITT M, LIFSON S. Refinement of protein conformations using a macromolecular energy minimization procedure [J]. Journal of Molecular Biology, 1969, 46, 269-279.
[115] FLECHER R, REEVES C M. Function minimization by conjugate gradients [J]. The Computer Journal, 1964, 7, 149-154.
[116] FLECHER R. Practical Methods of Optimization, Vol. 1, Unconstrained Optimization, 1980, John Wiley & Sons, New York.
[117] POWELL M J D. Restart procedures for the conjugate gradient method [J]. Mathematical Programming, 1977, 12, 241-254.
[118] GUNSTEREN W F, KARPLUS M. A method for constrained energy minimization of macromolecules [J]. Journal of Computationl Chemistry, 1980, 1, 266-274.
[119] BROYDEN C G. The Convergence of a Class of Double-rank Minimization Algorithms [J]. Journal of International Mathematical. Application, 1970, 6, 222-231
[120] FLECHER R. A new approach to variable metric algorithms [J]. The Computer Journal, 1970, 13, 317-322.
[121] GOLDFARB, D. A Family of Variable Metric Updates Derived by Variational Means [J]. Mathematics of Computing, 1970, 24, 23-26.
[122] SHANNO, D. F. Conditioning of Quasi-Newton Methods for Function Minimization [J]. Mathematics of Computing, 1970, 24, 647-656.
[123] FERMI E, PASTA J, ULAM S. Collected Papers of Enrico Fermi. Edited by Segre E. Chicago: University of Chicago Press, 1965.
[124] ALDER B J, WAINWRIGHT T E. Studies in Molecular Dynamics. I. General Method [J]. Journal of Chemical Physics, 1959, 31, 459-467.
[125] RAHMAN A. Correlations in the Motion of Atoms in Liquid Argon [J]. Physical Review, 1964, 136: A405-A411.
[126] VERLET L. Computer "Experiments" on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules [J]. Physcal Review, 1967, 159: 98-103.
[127] DUAN Y, KOLLMAN P A. Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution [J]. Science, 1998, 282: 740-744.
[128] ZHONG Q, JIANG Q, MOORE P B, et al. Molecular dynamics simulation of a synthetic ion channel [J]. Biophysical Journal, 1998, 74: 3-10.
[129] ZHONG Q, MOORE P B, NEWNS D M, et al. Molecular dynamics study of the LS3 voltage-gated ion channel [J]. FEBS Letter, 1998, 427: 267-270.
[130] MI H, TUCKERMAN M E, SCHUSTER D I, et al. A molecular dynamics study of HIV-1 protease complexes with C60 and fullerene-based anti-viral agents [J]. Proceedings of the Electrochemical Society, 1999, 99, 256-269.
[131] TUCKERMAN M E, MARTYNA G. J. Understanding Modern Molecular Dynamics: Techniques and Applications [J]. Journal of Physics Chemistry B, 2000, 104: 159-178.
[132] BEEMAN D. Some Multistep Methods for Use in Molecular Dynamics Calculations [J]. Journal of Computational Chemistry, 1976, 20, 130-139.
[133] VERLET L. Computer "Experiments" on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules [J]. Physical Review, 1963, 159: 98-103.
[134] HOOVER W G. Canonical dynamics: Equilibrium phase-space distributions [J]. Physical Review A, 1985, 31: 1695-1697.
[135] NOSE S, KLEIN M L. Constant pressure molecular dynamics for molecular systems [J]. Molecular Physics, 1983, 50: 1055-1076.
[136] NOSE S. A molecular dynamics method for simulations in the canonical ensemble [J]. Molecular Physics, 1984, 53: 255-268.
[137] NOSE S, YONEZAWA F. Isothermal–isobaric computer simulations of melting and crystallization of a Lennard-Jones system [J]. Journal of Chemical Physics, 1986, 84: 1803-1815.
[138] HAILE J M, GRABEN H W. Molecular dynamics simulations extended to various ensembles. I. Equilibrium properties in the isoenthalpic–isobaric ensemble [J]. Journal of Chemical Physics, 1980, 73: 2412-2420.
[139]徐筱杰.计算机辅助药物分子设计[M].北京:化学工业出版社,2004.
[140] KUNTZ I D. Structure-based strategies for drug design and discovery [J]. Science, 257, 1992: 1078-1082.
[141] KUNTZ I D, AGARD D A. Assessment of the role of computations in structural biology [J]. Advance in Protein Chemistry, 2003, 66: 1-25.
[142] MENG E C, GSCHWEND D A, BLANEY J M, et al. Orientational sampling and rigid-body minimization in molecular docking [J]. Proteins, 1993, 17: 266-278.
[143] MORRIS G. M, GOODSELL D S, HUEY R, et al. Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4 [J]. Journal of Computational Aided Molecular Design, 1996, 10: 293-304.
[144] GOODSELL D S, OLSON A J. Automated docking of substrates to proteins by simulated annealing [J]. Proteins, 1990, 8: 195-202.
[145] OSTERBERG F, MORRIS G. M, SANNER M F, et al. Automated docking to multiple target structures: incorporation of protein mobility and structural water heterogeneity in AutoDock [J]. Proteins, 2002, 46: 34-40.
[146] KION A E, GLICK M, THOMA M, et al. Finding more needles in the haystack: A simple and efficient method for improving high-throughput docking results[J]. Journal of Medicinal Chemistry, 2004, 47: 2743-2749.
[147] LUTY B A, WASSERMAN Z R, STOUTEN P F W, et al. A molecular mechanics/grid method for evaluation of ligand-receptor interactions [J]. Journal of Computational Chemistry, 1995, 16, 454-464.
[148]唐敖庆.量子化学[M].北京:科学出版社, 1982
[149]唐敖庆,杨忠志.大分子体系的量子化学[M].长春:吉林大学出版社,2000.
[150]田安民.量子化学[M].四川:四川大学出版社,1989.
[151]廖沐真.量子化学从头计算方法[M].北京:清华大学出版社,1989.
[152]江逢霖.量子化学原理[M].上海:复旦大学出版社,1990.
[153] SLATER J C. Quantum Theory of Molecular and Solids. Vol. 4: The Self-Consistent Field for Molecular and Solids McGraw-Hill: New York, 1974.
[154] SALAHUB D R, ZERNER M C. The Challenge of d and f Electrons ACS: Washington, D.C. 1989
[155] PARR R G, YANG W. Density-functional theory of atoms and molecules Oxford Univ. Press: Oxford, 1989
[156] WRIGHT J R. Immunoregulatory functions of surfactant proteins [J]. Nature Reviews Immunology, 2005, 5: 58-68.
[157] ERPENBECK V J, KRUG N, HOHLFELD J M. Therapeutic use of surfactant components in allergic asthma [J]. Naunyn-Schmiedeberg’s Archives of Pharmacology, 2009, 379: 217-224.
[158] KINGMA P S, WHITSETT J A. In defense of the lung: surfactant protein A and surfactant protein D [J]. Current Opinion in Pharmacology, 2006, 6: 277-283.
[159] VIGERUST D J, SHEPHERD V L. Virus glycosylation: role in virulence and immune interactions [J]. TRENDS in Microbiology, 2007, 15: 211-218.
[160] GUPTA G, SUROLIA A. Collectins: sentinels of innate immunity [J]. Bioessays, 2007, 29: 452-464.
[161] KISHORE U, GREENHOUGH T J, WATERS P, SHRIVE A K, GHAI R, KAMRAN M F, BERNAL A L, REID K B M, MADAN T, CHAKRABORTY T. Surfactant protein SP-A and SP-D: Structure, function and receptors [J]. Molecular Immunology, 2006, 43: 1293-1315.
[162] PASTVA A M, WRIGHT J R, WILLIAMS K L. Immunomodulatory Roles of Surfactant Proteins A and D: Implications in Lung Disease [J]. Preceedings of the American Thoracic Society, 2007, 4: 252-257.
[163] HACZKU A. Protective role of the lung collectins surfactant protein A and surfactant protein D in airway inflammation [J]. Journal of Allergy and Clinical Immunology, 2008, 122: 861-879.
[164] DAHL M. Biomarkers for Chronic Obstructive Pulmonary Disease: Surfactant Protein D and C-Reactive Protein [J]. American Journal of Respiratory and Critical Care Medicine, 2008, 177: 1177-1178.
[165] HARTSHORN K L, CROUCH E C, WHITE M R, EGGLETON P, TAUBER A I, CHANG D, SASTRY K. Evidence for a Protective Role of Pulmonary Surfactant Protein D (SP-D) against Influenza A Viruses [J]. Journal of Clinical Investigation, 1994, 94: 311-319.
[166] HARTSHORN K L, WEBBY R, WHITE M R, TECLE T, PAN C, BOUCHER S, MORELAND R J, CROUCH E C, SCHEULE R K. Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D [J]. Respiratory Research, 2008, 9: 65-76.
[167] CROUCH E, HARTSHORN K, HORLACHER T, MCDONALD B, SMITH K, CAFARELLA T, SEATON B, SEEBERGER P H, HEAD J. Recognition of Mannosylated Ligands and Influenza A Virus by Human Surfactant Protein D: Contributions of an Extended Site and Residue 343 [J]. Biochemistry, 2009, 48: 3335-3345.
[168] MESCHI J, CROUCH E C, SKOLNIK P, YAHYA K, HOLMSKOV U, LETH-LARSEN R, TORNOE I, TECLE T, WHITE M R, HARTSHORN K L. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication [J]. Journal of General Virology, 2005, 86: 3097-3107.
[169] HOLMSKOV U L. Collectins and collectin receptors in innate immunity [J]. APMIS Suppl, 2000, 100: 1-59.
[170] KUROKI Y, VOELKER D R. Pulmonary Surfactant Proteins [J]. Journal ofBiological Chemistry, 1994, 269: 25943-25946.
[171] PERSSON A, CHANG D, CROUCH E. Surfactant Protein D Is a Divalent Cation-dependent Carbohydrate-binding Protein [J]. Journal of Biological Chemistry, 1990, 265: 5755-5760.
[172] CROUCH E, MCDONALD B, SMITH K, ROBERTS M, MEALY T, SEATON B, HEAD J. Critical Role of Arg/Lys343 in the Species-Dependent Recognition of Phosphatidylinositol by Pulmonary Surfactant Protein D [J]. Biochemistry, 2007, 46: 5160-5169.
[173] NIE X, NISHITANI C, YAMAZOE M, ARIKI S, TAKAHASHI M, SHIMIZU T, MITSUZAWA H, SAWADA K, SMITH K, CROUCH E, NAGAE H, TAKAHASHI H, KUROKI Y. Pulmonary Surfactant Protein D Binds MD-2 through the Carbohydrate Recognition Domain [J]. Biochemistry, 2008, 47: 12878-12885.
[174] SHRIVE A K, THARIA H A, STRONG P, KISHORE U, BURNS I, RIZKALLAH P J, REID K B M, GREENHOUGH T J. High-resolution Structural Insights into Ligand binding and Immune Cell Recognition by Human Lung Surfactant Protein D [J]. Journal of Biological Chemistry, 2003, 331: 509-523.
[175] CROUCH E C, SMITH K, MCDONALD B, BRINER D, LINDERS B, MCDONALD J, HOLMSKOV U, HEAD J, HARTSHORN K. Species Differences in the Carbohydrate Binding Preferences of Surfactant Protein D [J]. American Journal of Respiratory Cell and Molecular Biology, 2006, 35: 84-94.
[176] PERSSON A V, GIBBONS B J, SHOEMAKER J D, MOXLEY M A, LONGMORE W J. The Major Glycolipid Recognized by SP-D in Surfactant Is Phosphatidylinositol [J]. Biochemistry, 1992, 31: 12183-12189.
[177] OGASAWARA Y, KUROKI Y, AKINO T. Pulmonary Surfactant Protein D Specifically Binds to Phosphatidylinositol [J]. Journal of Biological Chemistry, 1992, 267: 21244-21249.
[178] LU J, WILLIS A C, REID K B M. Purification, characterization and cDNA cloning of human lung surfactant protein D [J]. Biochemical Journal, 1992, 284:795-802.
[179] THORMANN E, DREYER J K, SIMONSEN A C, HANSEN P L, HANSEN S, HOLMSKOV U, MOURITSEN O G. Dynamic Strength of the Interaction between Lung Surfactant Protein D (SP-D) and Saccharide Ligands [J]. Biochemistry, 2007, 46: 12231-12237.
[180] Discovery Studio 2.1, San Diego: Accelrys, CA 92121, USA, 2008.
[181] WU G, ROBERTSON D H, BROOKS III C L, VIETH M. Detailed Analysis of Grid-Based Molecular Docking: A Case Study of CDOCKER—A CHARMm-Based MD Docking Algorithm [J]. Journal of Computational Chemistry, 2003, 24: 1549-1562.
[182] PHILLIPS J C, BRAUN R, WANG W, GUMBART J, TAJKHORSHID E, VILLA E, CHIPOT C, SKEEL R D, KALéL, SCHULTEN K. Scalable Molecular Dynamics with NAMD [J]. Journal of Computational Chemistry, 2005, 26: 1781-1802.
[183][29] GUVENCH O, GREENE S N, KAMATH G, BRADY J W, VENABLE R M, PASTOR R W, MACKERELL A D, JR. Additive Empirical Force Field for Hexopyranose Monosaccharides [J]. Journal of Computational Chemistry, 2008, 29: 2543-2564.
[184] HUMPHREY W, DALKE A, SCHULTEN K. VMD: Visual Molecular Dynamics [J]. Journal of Molecular Graphics, 1996, 14: 33-38.
[185] JORGENSEN W L, CHANDRASEKHAR J, MADURA J D, IMPEY R W, KLEIN M L. Comparison of simple potential functions for simulating liquid water [J]. Journal of Chemical Physics, 1983, 79: 926-935.
[186] DARDEN T, YORK D, PEDERSEN L. Particle mesh Ewald: An N?log(N) method for Ewald sums in large systems [J]. Journal of Chemical Physics, 1993, 98: 10089-10092.
[187] TOUKMAJI A Y, BOARD J J A. Ewald summation techniques in perspective: a survey [J]. Computer Physics Communications, 1996, 95: 73-92.
[188] FELLER S E, ZHANG Y, PASTOR R W. Constant pressure molecular dynamics simulation: The Langevin piston method [J]. Journal of ChemicalPhysics, 1995, 103: 4613-4621.
[189] LU H, ISRALEWITZ B, KRAMMER A, VOGEL V, SCHULTEN K. Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation [J]. Biophysical Journal, 1998, 75(2): 662-671.
[190] ZHANG Q, LU Z, HU H, YANG W, MARSZALEK P E. Direct Detection of the Formation of V-Amylose Helix by Single Molecule Force Spectroscopy [J]. Journal of the American Chemical Society, 2006, 128(29): 9387-9393.
[191] ZHANG D, GULLINGSRUD J, MCCAMMON J A. Potentials of Mean Force for Acetylcholine Unbinding from the Alpha7 Nicotinic Acetylcholine Receptor Ligand-Binding Domain [J]. Journal of the American Chemical Society, 2006, 128(9): 3019-3026.
[192] LIU X, XU Y, WANG X, BARRANTES F J, JIANG H. Unbinding of Nicotine from the Acetylcholine Binding Protein: Steered Molecular Dynamics Simulations [J]. Journal of Physical Chemistry B, 2008, 112(13):4087-4093.
[193] DARVE E, POHORILLE A. Calculating free energies using average force [J]. Journal of Chemical Physics, 2001, 115: 9169-9183.
[194] DEN OTTER W K. Thermodynamic integration of the free energy along a reaction coordinate in Cartesian coordinates [J]. Journal of Chemical Physics, 2000, 112: 7283-7292.
[195] HéNIN J, CHIPOT C. Overcoming free energy barriers using unconstrained molecular dynamics simulations [J]. Journal of Chemical Physics, 2004, 121: 2904-2914.
[196] BARTELS C, KARPLUS M. Multidimensional adaptive umbrella sampling: Applications to main chain and side chain peptide conformations [J]. Journal of Computational Chemistry, 1997, 18(12): 1450-1462.
[197] BARTELS C, KARPLUS M. Probability Distributions for Complex Systems: Adaptive Umbrella Sampling of the Potential Energy [J]. Journal of Physical Chemistry B, 1998, 102(5): 865-880.
[198] RODRIGUEZ-GOMEZ D, DARVE E, POHORILLE A. Assessing the efficiency of free energy calculation methods [J]. Journal of Chemical Physics,2004, 120(8): 3563-3578.
[199] IZRAILEV S, STEPANIANTS S, BALSERA M, OONO Y, SCHULTEN K. Molecular dynamics study of unbinding of the avidin-biotin complex [J]. Biophysical Journal, 1997, 72(4): 1568-1581.
[200] ISRALEWITZ B, IZRAILEV S, SCHULTEN K. Binding pathway of retinal to bacterio-opsin: a prediction by molecular dynamics simulations [J]. Biophysical Journal, 1997, 73(6): 2972-2979.
[201] KOSZTIN D, IZRAILEV S, SCHULTEN K. Unbinding of Retinoic Acid from its Receptor Studied by Steered Molecular Dynamics [J]. Biophysical Journal, 1999, 76(1): 188-197.
[202] GRUBMüLLER H, HEYMANN B, TAVAN P. Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force [J]. Science, 1996, 271: 997-999.
[203] SEBOLT-LEOPOLD J S, HERRERA R. Targeting the mitogen-activated protein kinase cascade to treat cancer [J]. Nature Reviews Cancer, 2004, 4(12): 937-947.
[204] SMALLEY K S M. A pivotal role for ERK in the oncogenic behaviour of malignant melanoma? [J]. International Journal of Cancer, 2003, 104(5): 527-532.
[205] KOHNO M, POUYSSEGUR J. Targeting the ERK signaling pathway in cancer therapy [J]. Annals of Medicine, 2006, 38(3): 200-211.
[206] HILGER R A, SCHEULEN M E, STRUMBERG D. The Ras-Raf-MEK-ERK pathway in the treatment of cancer [J]. Onkologie, 2002, 25(6): 511-518.
[207] LEFLOCH R, POUYSSEGUR J, LENORMAND P. Total ERK1/2 activity regulates cell proliferation [J]. Cell Cycle, 2009, 8(5):705-711.
[208] CHAMBARD J C, LEFLOCH R, POUYSSEGUR J, LENORMAND P. ERK implication in cell cycle regulation [J]. Biochimica et Biophysica Acta-Molecular Cell Research, 2007, 1773(8):1299-1310.
[209] HERRERA R, SEBOLT-LEOPOLD J S. Unraveling the complexities of the Raf/MAP kinase pathway for pharmacological intervention [J]. Trends inMolecular Medicine, 2002, 8(4): S27-S31.
[210] KYRIAKIS J M, AVRUCH J. Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation [J]. Physiological Reviews, 2001, 81(2): 807-869.
[211] HO A K, HASHIMOTO K, CHIK C L. 3',5'-Cyclic Guanosine Monophosphate Activates Mitogen-Activated Protein Kinase in Rat Pinealocytes [J]. Journal of Neurochemistry, 1999, 73(2):598-604.
[212] LEFLOCH R, POUYSSEGUR J, LENORMAND P. Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels [J]. Molecular and Cellular Biology, 2008, 28(1): 511-527.
[213] ARONOV A M, BAKER C, BEMIS G W, CAO J R, CHEN G J, FORD P J, GERMANN U A, GREEN J, HALE M R, JACOBS M, JANETKA J W, MALTAIS F, MARTINEZ-BOTELLA G, NAMCHUK M N, STRAUB J, TANG Q, XIE X L. Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors [J]. Journal of Medicinal Chemistry, 2007, 50(6):1280-1287.
[214] HU G D, ZHANG S L, ZHANG Q G. Molecular Dynamics Simulations and Free Energy Calculation of FKBP12 Protein and Its Inhibitors [J]. Acta Chimica Sinica, 2009, 67(9): 1019-1025.
[215] MA G Z, LIU C, QIU Y F, NAN J M. Minor Groove Binding between DB818 and DNA: a Molecular Dynamics Simulation and Binding Free Energy Analysis [J]. Acta Chimica Sinica, 2009, 67(5): 453-458.
[216] DE GROOT C O, JELESAROV I, DAMBERGER F F, BJELIC S, SCHARER M A, BHAVESH N S, GRIGORIEV I, BUEY R M, WUTHRICH K, CAPITANI G, AKHMANOVA A, STEINMETZ M O. Molecular Insights into Mammalian End-binding Protein Heterodimerization [J]. Journal of Biological Chemistry, 2010, 285(8): 5802-5814.
[217] DAL BEN D, ANTONINI I, BUCCIONI M, LAMBERTUCCI C, MARUCCI G, VITTORI S, VOLPINI R, CRISTALLI G. Molecular Modeling Studies on theHuman Neuropeptide S Receptor and Its Antagonists [J]. ChemMedChem, 2010, 5(3): 371-383.
[218] BHUIYAN M A, ISHIGURO M, HOSSAIN M, NAKAMURA T, OZAKI M, MIURA S, NAGATOMO T. Binding sites of valsartan, candesartan and Iosartan with angiotensin II receptor 1 subtype by molecular modeling [J]. Life Sciences, 2009, 85(3-4): 136-140.
[219] Insight II, Molecular Simulation Inc. San Diego, 2000.
[220] MORRIS A L, MACARTHUR M W, HUTCHINSON E G, THORNTON J M. Stereochemical quality of protein structure coordinates [J]. Proteins, 1992, 12(4): 345-364.
[221] FOLOPPE N, FISHER L M, HOWES R, KIERSTAN P, POTTER A, ROBERTSON A G S, SURGENOR A E. Structure-based design of novel Chk1 inhibitors: Insights into hydrogen bonding and protein-ligand affinity [J]. Journal of Medicinal Chemistry, 2005, 48(18): 4332-4345.
[222] KRISHNAMURTHY V M, KAUFMAN G K, URBACH A R, GITLIN I, GUDIKSEN K L, WEIBEL D B, WHITESIDES G M. Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein?Ligand Binding [J]. Chemical Reviews, 2008, 108(3): 946-1051.
[223] SCOZZAFAVA A, MASTROLORENZO A, SUPURAN C T. Carbonic anhydrase inhibitors and activators and their use in therapy [J]. Expert Opinion On Therapeutic Patents, 2006, 16(12):1627-1664.
[224] PASTOREKOVA S, PARKKILA S, PASTOREK J, SUPURAN C T. Carbonic anhydrases: Current state of the art, therapeutic applications and future prospects [J]. Journal of Enzyme Inhibition and Medicinal Chemistry, 2004, 19(3):199-229.
[225] SUPURAN C T, SCOZZAFAVA A. Applications of carbonic anhydrase inhibitors and activators in therapy [J]. Expert Opinion On Therapeutic Patents, 2002, 12(2): 217-242.
[226] SUPURAN C T, CASINI A, SCOZZAFAVA A. Protease inhibitors of the sulfonamide type: Anticancer, antiinflammatory, and antiviral agents [J].Medicinal Research Reviews, 2003, 23(5): 535-558.
[227] SCHUMAN J S. Short- and long-term safety of glaucoma drugs [J]. Expert Opin Drug Saf, 2002, 1(2): 181-194.
[228] SUPURAN C T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators [J]. Nature Reviews Drug Discovery, 2008, 7(2): 168-181.
[229] WINUM J Y, RAMI M, SCOZZAFAVA A, MONTERO J L, SUPURAN C. Carbonic anhydrase IX: A new druggable target for the design of antitumor agents [J]. Medicinal Research Reviews, 2008, 28(3): 445-463.
[230] DI FIORE A, MONTI S M, HILVO M, PARKKILA S, ROMANO V, SCALONI A, PEDONE C, SCOZZAFAVA A, SUPURAN C T, DE SIMONE G. Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide [J]. Proteins-Structure Function and Bioinformatics, 2009, 74(1):164-175.
[231] KHALIFAH R G. The Carbon Dioxide Hydration Activity of Carbonic Anhydrase: I. STOP-FLOW KINETIC STUDIES ON THE NATIVE HUMAN ISOENZYMES B AND C [J]. Journal of Biological Chemistry, 1971, 246: 2561-2573.
[232] ELDER I, FISHER Z, LAIPIS P J, TU C, MCKENNA R, SILVERMAN D N. Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III [J]. Proteins-Structure Function and Bioinformatics, 2007, 68(1): 337-343.
[233] HILVO M, BARANAUSKIENE L, SALZANO A M, SCALONI A, MATULIS D, INNOCENTI A, SCOZZAFAVA A, MONTI S M, DI FIORE A, DE SIMONE G, LINDFORS M, JANIS J, VALJAKKA J, PASTOREKOVA S, PASTOREK J, KULOMAA M S, NORDLUND H R, SUPURAN C T, PARKKILA S. Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes [J]. Journal of Biological Chemistry, 2008, 283(41): 27799-27809.
[234] MONTGOMERY J C, VENTA P J, EDDY R L, FUKUSHIMA Y S, SHOWS TB, TASHIAN R E. Characterization of the human gene for a newly discovered carbonic anhydrase, CA VII, and its localization to chromosome 16 [J]. Genomics, 1991, 11(4): 835-848.
[235] HALMI P, PARKKILA S, HONKANIEMI J. Expression of carbonic anhydrases II, IV, VII, VIII and XII in rat brain after kainic acid induced status epilepticus [J]. Neurochemistry International, 2006, 48(1):24-30.
[236] RUUSUVUORI E, LI H, HUTTU K, PALVA JM, SMIRNOV S, RIVERA C, KAILA K, VOIPIO J. Carbonic anhydrase isoform VII acts as a molecular switch in the development of synchronous gamma-frequency firing of hippocampal CA1 pyramidal cells [J]. Journal of Neuroscience, 2004, 24(11):2699-2707.
[237] RIVERA C, VOIPIO J, KAILA K. Two developmental switches in GABAergic signalling: the K+-Cl- cotransporter KCC2 and carbonic anhydrase CAVII [J]. Journal of Physiology-London, 2005, 562(1): 27-36.
[238] GüZEL ?, INNOCENTI A, SCOZZAFAVA A, SALMAN A, SUPURAN CT. Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors [J]. Bioorganic & Medicinal Chemistry Letters, 2009, 19(12): 3170-3173.
[239] Insight II User Guide, San Diego:Biosym/MSI (2000)
[240] SAAM J, IVANOV I, WALTHER M, HOLZHUETTER H G, KUHN H. Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels [J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(33):13319-13324.
[241] Gaussian 03, Revision E.01 [M], Gaussian, Inc., Pittsburgh PA, (2003).
[242] Insight II Homology User Guide, San Diego: Accelrys Inc (2000).
[243] ALTSCHUL S F, MADDEN T L, SCHAFFER A A, ZHANG J, ZHANG Z, MILLER W, LIPMAN D J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J]. Nucleic Acids Res, 1997, 25(17):3389-3402.
[244] SALI A, OVERINGTON J P. Derivation of rules for comparative protein modeling from a database of protein structure alignments [J]. Protein Sci, 1994, 3(9): 1582-1596.
[245] SALI A, POTTERTON L, YUAN F, VAN VLIJMEN H, KARPLUS M. Evaluation of comparative protein modeling by MODELLER [J]. Proteins, 1995, 23(3): 318-326.
[246] SALI A. Modeling mutations and homologous proteins [J]. Current Opinion in Biotechnology, 1995, 6(4):437-451.
[247] Insight II Profile-3D User Guide, San Diego: Biosym/MSI (2000).
[248] LASKOWSKI R A, MOSS D S, THORNTON J M. Main-chain bond lengths and bond angles in protein structures [J]. Journal of Molecular Biology, 1993, 231(4): 1049-1067.
[249] KOLLMAN P A, MASSOVA I, REYES C, KUHN B, HUO S H, CHONG L, LEE M, LEE T, DUAN Y, WANG W, DONINI O, CIEPLAK P, SRINIVASAN J, CASE D A, CHEATHAM T E. Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models [J]. Accounts of Chemical Research, 2000, 33(12): 889-897.
[250] HüNENBERGER PH, HELMS V, NARAYANA N, TAYLOR SS, MCCAMMON JA. Determinants of Ligand Binding to cAMP-Dependent Protein Kinase [J]. Biochemistry, 1999, 38(8): 2358-2366.
[251] SIROCKIN F, SICH C, IMPROTA S, SCHAEFER M, SAUDEK V, FROLOFF N, KARPLUS M, DEJAEGERE A. Structure Activity Relationship by NMR and by Computer: A Comparative Study [J] Journal of the American Chemical Society, 2002, 124(37): 11073-11084.
[252] KREBS H A. Inhibition of carbonic anhydrase by sulphonamides [J]. Biochemical Journal, 1948, 43: 525-528.
[253] DUDA D, GOVINDASAMY L, AGBANDJE-MCKENNA M, TU C, SILVERMAN DN, MCKENNA R. The refined atomic structure of carbonic anhydrase II at 1.05 angstrom resolution: implications of chemical rescue of proton transfer [J]. Acta Crystallographica Section D-BiologicalCrystallography, 2003, 59(1):93-104.
[254] VULLO D, INNOCENTI A, NISHIMORI I, PASTOREK J, SCOZZAFAVA A, PASTOREKOVáS, SUPURAN C T. Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides - a new target for the design of antitumor and antiglaucoma drugs? [J]. Bioorganic & Medicinal Chemistry Letters, 2005, 15(4):971-976.
[255] BORIACK-SJODIN P A, ZEITLIN S, CHEN H H, CRENSHAW L, GROSS S, DANTANARAYANA A, DELGADO P, MAY JA, DEAN T, CHRISTIANSON DW. Structural analysis of inhibitor binding to human carbonic anhydrase II [J]. Protein Science, 1998, 7: 2483-2489.