Recent Advances in Drug Discovery Research Using Structure-Based Virtual Screening Techniques: Examples of Success for Diverse Protein Targets

Drug Discovery Research: New Frontiers in the Post-Genomic Era

Volumn , Issue , 2006, Pages 24-62

  Ghosh, Sutapa ^a   Nie, Aihua ^a,b   An, Jing ^a,c,d   Huang, Ziwei ^a,c,e  

^a BURNHAM INSTITUTE   (United States)

^b BEIJING INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY   (China)

^c UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^d Chemokine Pharmaceutical Inc   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Docking based virtual screening and Hsp90 inhibitor; Knowledge based scoring functions; Virtual screening of chemical libraries

Indexed keywords

EID: 84889492535     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470131862.ch2     Document Type: Chapter

References (126)

1. MOE (2003). Montreal: Chemical Computing Group.
2. ICM (2005). La Jolla, CA: Molsoft LLC.
3. Ahrén, B., Simonsson, E., and Larsson, H. (2002). Islet hormone secretion under normal conditions in diabetes and in obesity. Diabetes Care 25, 869-875.
4. Asakura, M., Kitakaze, M., et al. (2002). Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: Metalloproteinase inhibitors as a new therapy. Nat Med 8, 35.
5. Bajorath, J. (2002). Integration of virtual and high-throughput screening. Nat Rev Drug Discov 1(11), 882-894.
6. Barril, X., Hubbard, R. E., and Morley, S. D. (2004). Virtual screening in structure-based drug discovery. Mini Rev Med Chem 4(7), 779-791.
7. Barril, X., Brough, P., Drysdale, M., Hubbard, R. E., Massey, A., Surgenor, A., and Wright., L. (2005). Structure-based discovery of a new class of Hsp90 inhibitors. Bioorg Med Chem Lett 15, 5187-5191.
8. Baxter, C. A., Murray, C.W., et al. (1998). Flexible docking using Tabu search and an empirical estimate of binding affinity. Proteins. 33(3), 367-382.
9. Beaudeux, J. L., Giral, P., et al. (2004). Matrix metalloproteinases, inflammation and atherosclerosis: Therapeutic perspectives. Clin Chem Lab Med. 42(2), 121-131.
10. Becker, O. M., Marantz, Y., et al. (2004). G protein-coupled receptors: In silico drug discovery in 3D. Proc Natl Acad Sci U S A. 101(31), 11304-11309.
11. Blundell T. L., J. H., and Abell, C. (2002). High-throughput crystallography for lead discovery in drug design. Nat Rev Drug Discov 1, 45-54.
12. Bohm, H. J. (1992). LUDI: Rule-based automatic design of new substituents for enzyme inhibitor leads. J Comput Aided Mol Des 6(6), 593-606.
13. Bohm, H. J. (1994). The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure. J Comput Aided Mol Des. 8(3), 243-256.
14. Bohm, H. J. (1998). Prediction of binding constants of protein ligands: A fast method for the prioritization of hits obtained from de novo design or 3D database search programs. J Comput Aided Mol Des 12(4), 309-23.
15. Borhani, D. W., Harters, T. M., and Petrash, J. M. (1992). The crystal structure of the aldose reductase NADPH binary complex. J Biol Chem 267, 24841-24847.
16. Bradshaw, R. A., and Yi, E. (2002). Methionine aminopeptidases and angiogenesis. Essays Biochem 38, 65-78.
17. Brooijmans, N., and Kuntz, I. D. (2003). Molecular recognition and docking algorithms. Ann Rev Biophys Biomol Struct 32, 335-373.
18. Carlson, H. A., and McCammon, J. A. (2000). Accommodating protein flexibility in computational drug design. Mol Pharmacol. 57(2), 213-218.
19. Cavasotto, C. N., Ortiz, M. A., et al. (2006). In silico identification of novel EGFR inhibitors with antiproliferative activity against cancer cells. Bioorg Med Chem Lett. Jan 11, Epub ahead of print.
20. Charifson, P. S., Corkery, J. J., Murcko, M. A., andWalters,W. P. (1999). Consensus scoring: A method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins. J Med Chem 42(25), 5100-5109.
21. Clark, D. E., Higgs, C., Wren, S. P., Dyke, H. J., Wong, M., Norman, D., Lockey, P. M., and Roach, A. G. (2004).Avirtual screening approach to finding novel and potent antagonists at the melanin-concentrating hormone 1 receptor, J Med Chem 47, 3962-3971.
22. Cosulich, S. C., Worrall, V., et al. (1997). Regulation of apoptosis by BH3 domains in a cell-free system. Curr Biol 7(12), 913-920.
23. Cvetkovic, R. S., and Perry, C.M. (2003). Brinzolamide: A review of its use in the management of primary open-angle glaucoma and ocular hypertension. Drugs Aging 20(12), 919-947.
24. Demutha, H. U., McIntoshb, C. H. S., and Pederson, R. A. (2005). Type 2 diabetes-Therapy with dipeptidyl peptidase IV inhibitors. Biochim Biophys Acta 1751, 33-44.
25. Desai, P. V., Patny, A., Sabnis, Y., Tekwani, B., Gut, J., Rosenthal, P., Srivastava, A., and Avery,M. (2004). Identification of novel parasitic cysteine protease inhibitors using virtual screening.1. The ChemBridge database. J Med Chem 47, 6609-6615.
26. Deveraux, Q. L., and Reed, J. C. (1999). IAP family proteins-Suppressors of apoptosis. Genes Dev 13, 239-252.
27. Di Marzo, V., Bifulco, M., and De Petrocellis, L. (2004). The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discovery 3, 771-784.
28. Di Nola, A., Roccatano, D., et al. (1994). Molecular dynamics simulation of the docking of substrates to proteins. Proteins 19(3), 174-182.
29. Doman, T. N., McGovern, S. L.,Witherbee, B. J., Kasten, T. P., Kurumbail, R., Stallings,W. C., Connolly, D. T., and Shoichet, B. K. (2002). Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B. J Med Chem 45, 2213-2221.
30. Eldridge, M. D., Murray, C. W., Auton, T. R., Paolini, G. V., and Mee, R. P. (1997). Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J Comput Aided Mol Des. 11(5), 425-445.
31. Engel, J. C., Doyel, P. S., Hseih, I., and McKerrow, J. H. (1998). Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J. Exp. Med. 188, 725-734.
32. Enyedy, I. J., Ling, Y., Nacro, K., Tomita, Y.,Wu, X., Cao, Y., Guo, R., Li, B., Zhu, X., and Huang, Y., et al. (2001). Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening. J Med Chem 44, 4313-4324.
33. Erik Sahai, C. J. M. (2002). Rho-GTPases and Cancer. Nat Rev Cancer 2(2), 133-142.
34. Eswaramoorthy, S., Kumaran, D., et al. (2002). A novel mechanism for Clostridium botulinum neurotoxin inhibition. Biochemistry 41(31), 9795-9802.
35. Etienne-Manneville, S., and Hall, A. (2002). Rho GTPases in cell biology Nature 420, 629-635.
36. Evers, A., and Klabunde, T. (2005). Structure-based drug discovery using GPCR homology modeling: Successful virtual screening for antagonists of the alpha1A adrenergic receptor. J Med Chem 48, 1088-1097.
37. Evers, A., and Klebe, G. (2004). Successful virtual screening for a submicromolar antagonist of the neurokinin-1 receptor based on a ligand-supported homology model. J Med Chem 47, 5381-5392.
38. Ewing, T. J., Makino, S., Skillman, A. G., and Kuntz, I. D. (2001). DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases. J Comput Aided Mol Des 15(5), 411-428.
39. Fan, K.,Wei, P., Feng, Q., Chen, S., Huang, C., Ma, L., Lai, B., Pei, J., Liu, Y., Chen, J., and Lai, L. (2004). Biosynthesis, purification and substrate specificity of SARS Coronavirus 3C-like proteinase. J Biol Chem 279, 1637-1642.
40. Fische, E. (1894). Einfluss der Configuration auf die wirkung der Enzyme. Ber Dt Chem Ges 27, 2985-2993.
41. Gao,Y., Dickerson, J. B., Guo, F., Zheng, J., and Zheng,Y. (2004). Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 101(20), 7618-7623.
42. Gaoni, Y., and Mechoulam, R. (1964). Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc. 86, 1646-1647.
43. Gibbs, J. B., and Oliff, A. (1997). The potential of farnesyltransferase inhibitors as cancer chemotherapeutics. Annu Rev Pharmacol Toxicol 37, 143-166.
44. Gohlke, H., Hendlich, M., and Klebe, G. (2000). Knowledge-based scoring function to predict protein-ligand interactions. J Mol Biol 295(2), 337-356.
45. Goodsell, D. S., Lauble, H., Stout, C. D., and Olson, A. J. (1993). Automated docking in crystallography: Analysis of the substrates of aconitase. Proteins 17(1), 1-10.
46. Hadfield, A. T., Diana, G. D., and Rossmann, M. G. (1999). Analysis of three structurally related antiviral compounds in complex with human rhinovirus 16. Proc Natl. Acad. Sci. U.S.A. 96, 14730-14735.
47. Halgren, T. A., Murphy, R. B., Friesner, R. A., Beard, H. S., Frye, L. L., Pollard, W. T., and Banks, J.L. (2004). Glide:Anewapproach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem. 47(7), 1750-1759.
48. Halperin, I., Ma, B., Wolfson, H., and Nussinov, R. (2002). Principles of docking: An overview of search algorithms and a guide to scoring functions. Proteins 47(4), 409-443.
49. Hart, T. N., and Read, R. J. (1992). A multiple-start Monte Carlo docking method. Proteins. 13(3), 206-222.
50. Hindle, S., Rarey, M., et al. (2002). Flexible docking under pharmacophore type constraints. J Comput Aided Mol Des 16(2), 129-149.
51. Irwin, J. J., Raushel, F. M., et al. (2005). Virtual screening against metalloenzymes for inhibitors and substrates. Biochemistry 44(37), 12316-12328.
52. Irwin, J. J., and Shoichet, B. K. (2005). ZINC-A free database of commercially available compounds for virtual screening. J Chem Inf Model 45(1), 177-182.
53. Jones, G., Willett, P., Glen, R. C., Leach, A. R., and Taylo, R. (1997). Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267(3), 727-748.
54. Kitchen, D. B., Decornez, H., et al. (2004). Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat Rev Drug Discov 3(11), 935-949.
55. Klabunde, T., and Hessler, G. (2002). Drug design strategies for targeting G-protein-coupled receptors. Chembiochem 3, 928-944.
56. Kohl, N. E., Mosser, S. D., et al. (1993). Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science 260, 1934-1937.
57. Kolatkar, P. R., Bella, J., Olson, N. H., Bator, C. M., and Baker, T. S., et al. (1999). Structural studies of two rhinovirus serotypes complexed with fragments of their cellular receptor. EMBO J 18, 6249-6259.
58. Kraemer, O., Hazemann, I., Podjarny, A. D., and Klebe, G. (2004).Virtual screening for inhibitors of human aldose reductase. Proteins: Struct Funct Bioinf 55, 814-823.
59. Kramer, B., Metz, G., Rarey, M., and Lengauer, T. (1999a). Ligand docking and screening with FlexX. Med Chem Res 9, 463-478.
60. Kramer, B., Rarey, M., and Lengauer, T. (1999b). Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking. Proteins 37(2), 228-241.
61. Kruger, E. A., and Figg, W. D. (2000). TNP-470: An angiogenesis inhibitor in clinical development for cancer. Expert Opin Investig Drugs 9(6), 1383-1396.
62. Lambeir, A. M., Durinx, C., Scharpe, S., and DeMeester, I. (2003). Dipeptidylpeptidase IV from bench to bedside: An update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 40, 209-294.
63. Leach, A. R. (1994). Ligand docking to proteins with discrete side-chain flexibility. J Mol Biol 235(1), 345-356.
64. Leach, A. R. (1996). Molecular Modeling: Principles and Applications. Harlow, UK: Addison-Wesley, Longman Limited.
65. Lee, N., Hui, D.,Wu, A., Chan, P., Cameron, P., Joynt, G. M., Ahuja, A.,Yung, M.Y., Leung, C. B., To,K. F., Lui, S. F., Szeto, C. C., Chung, S., and Sung, J. J. (2003). A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348, 1986.
66. Li, C., Xu, L., Wolan, D. W., Wilson, I. A., and Olson, A. J. (2004). Virtual screening of human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase against the NCI diversity set by use of AutoDock to identify novel nonfolate inhibitors. J Med Chem 47, 6681-6690.
67. Liu, Z., Huang, C., Fan, K., Wei, P., Chen, H., Liu, S., Pei,J., Shi, L., Li, B., Yang, K., Liu, Y., and Lai, L. (2005). Virtual screening of novel noncovalent inhibitors for SARS-CoV 3C-like proteinase. J Chem Inf Model 45, 10-17.
68. Lugovskoy, A. A., Degterev, A. I., Fahmy, A. F., Zhou, P., Gross, J. D., Yuan, J., andWagner, G. (2002). A novel approach for characterizing protein ligand complexes: Molecular basis for specificity of smallmolecule Bcl-2 inhibitors. J Am Chem Soc. 124, 1234-1240.
69. Lyne, P. D., Kenny, P. W., et al. (2004). Identification of compounds with nanomolar binding affinity for checkpoint kinase-1 using knowledge-based virtual screening. J Med Chem 47(8), 1962-1968.
70. Maloney, A., and Workman, P. (2002). HSP90 as a new therapeutic target for cancer therapy: The story unfolds. Expert Opin Biol Ther 2(1), 3-24.
71. McGann, M. R., Almond, H. R., Nicholls, A., Grant, J. A., and Brown, F. K. (2003). Gaussian docking functions. Biopolymers 68(1), 76-90.
72. Meng, E. C., Shoichet, B. K., et al. (1992). Automated docking with grid-based energy evaluation. J Comp Chem 13, 505-524.
73. Mira, J. P., Benard,V., Groffen, J., Sanders, L. C., and Knaus, U. G.. (2000). Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. Proc Natl Acad Sci USA 97(1), 185-189.
74. Mizutani, M. Y., and Itai, A. (2004). Efficient method for high-throughput virtual screening based on flexible docking: Discovery of novel acetylcholinesterase inhibitors. J Med Chem 47, 4818-4828.
75. Møller, N. P., Iversen, L. F., Andersen, H. S., and McCormack, J. G. (2000). Protein tyrosine phosphatases (PTPs) as drug targets: Inhibitors of PTP-1B for the treatment of diabetes. Curr Opin Drug Discovery 3, 527-540.
76. Mosselman, S., Polman, J., and Dijkema, R. (1996). ER beta: Identification and characterization of a novel human estrogen receptor. FEBS Lett. 392, 49-53.
77. Muegge, I. (2000). A knowledge-based scoring function for protein-ligand interactions: Probing the reference state. Perspect Drug Discov Des 20, 99-114.
78. Muegge, I. (2001). Effect of ligand volume correction on PMF scoring. J Comput Chem 22(4), 418-425.
79. Muegge, I., and Martin, Y. C. (1999). A general and fast scoring function for protein-ligand interactions: A simplified potential approach. J Med Chem 42(5), 791-804.
80. Muegge, I., and I. Enyedy (2004). Docking and scoring. In J. Tollenaere,H.DeWinter,W. Langenaeker and P. Bultinck (Eds.), Computational Medicinal Chemistry and Drug Discovery.NewYork: Marcel Dekker, pp. 405-436.
81. Nikolovska-Coleska, Z., Xu, L., Hu, Z., Tomita, Y., Li, P., Roller, P. P., Wang, R., Fang, X., Guo, R., and Zhang, M., et al. (2004). Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. J Med Chem 47(10), 2430-2440.
82. Normanno, N., Bianco, C., et al. (2005). The ErbB receptors and their ligands in cancer: An overview. Curr Drug Targets 6, 243-257.
83. Oefner, C., D-Arcy, A., MacSweeney, A., Pierau, S., Gardiner, R., and Dale, G. E. (2003). High-resolution structure of human apo dipeptidyl peptidase IV/CD26 and its complex with 1-[([2-[(5-iodopyridin-2-yl)amino]-ethyl]amino)-acetyl]-2-cyano-(S)-pyrrolidine. Acta Crystallogr DBiol Crystallogr 59, 1206-1212.
84. Oh, M., Im, I., Lee, Y. J., Kim, Y. H., Yoon, J. H., Park, H. G, Higashiyama, S., Kima,Y. C., and Parka,W. J. (2004). Structure-based virtual screening and biological evaluation of potent and selective ADAM12 inhibitors. Bioorg Med Chem Lett 14, 6071-6074.
85. Oshiro, C. M., Kuntz, I. D., et al. (1995). Flexible ligand docking using a genetic algorithm. J Comput Aided Mol Des 9(2), 113-130.
86. Park, H.W., Boduluri, S. R., Moomaw, J. F., Casey, P. J., and Beese, L. S. (1997). Crystal structure of protein farnesyltransferase at 2.25 angstrom resolution. Science 275, 1800-1804.
87. Perola, E., Xu, K.,Kollmeyer, T. M., Kaufmann, S. H., Prendergast, F. G., and Pang,Y. P. (2000). Successful virtual screening of a chemical database for farnesyltransferase inhibitor leads. J Med Chem 43, 401-408.
88. Prendergast, G. C., J. P. Davide, et al. (1994). Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Mol Cell Biol 14, 4193-4202.
89. Puius,Y. A., Zhao,Y., Sullivan, M., Lawrence, D. S., Almo, S. C., and Zhang, Z. Y. (1997). Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: A paradigm for inhibitor design. Proc Natl Acad Sci USA 94, 13420-13425.
90. Rarey, M., Kramer, B., Lengauer, T., and Klebe, G. (1996). A fast flexible docking method using an incremental construction algorithm. J Mol Biol 261(3), 470-489.
91. Rasmussen, H. B., Branner, S., Wiberg, F. C., and Wagtmann, N. (2003). Different modes of dipeptidyl peptidase IV (CD26) inhibition by oligopeptides derived from the N-terminus of HIV-1 Tat indicate at least two inhibitor binding sites. Nat Struct Biol 10, 19-25.
92. Rollinger, J. M., Hornick, A., Langer, S., and Prast, H. (2004). Acetylcholinesterase inhibitory activity of scopolin and scopoletin discovered by virtual screening of natural products. J Med Chem 47, 6248-6254.
93. Rota, P. A., Oberste, M. S., Monroe, S. S., Nix, W. A., Campagnoli, R., Icenogle, J. P., Penaranda, S., Bankamp, B., Maher, K., Chen, M. H., Tong, S., Tamin, A., Lowe, L., Frace, M., DeRisi, J. L., Chen, Q., Wang, D., Erdman, D. D., Peret, T. C., Burns, C., Ksiazek, T. G., Rollin, P. E., Sanchez, A., Liffick, S., Holloway, B., Limor, J., McCaustland, K., Olsen-Rasmussen, M., Fouchier, R., Gunther, S., Osterhaus, A. D., Drosten, C., Pallansch, M. A., Anderson, L. J., and Bellini, W. J. (2003). Characterization of a novel Coronavirus associated with severe acute respiratory syndrome. Science 300, 1394-1399.
94. Sajid, M., and McKerrow, J. (2002). Cysteine proteases of parasitic organisms. Mol Biochem Parasitol 120, 1-21.
95. Salo, O. M. H., Raitio, K. H., Savinainen, J. R., Nevalainen, T., Lahtela-Kakkonen, M., Laitinen, J. T., Järvinen, T., and Poso, A. (2005). Virtual screening of novel CB2 ligands using a comparative model of the human cannabinoid CB2 receptor. J Med Chem 48, 7166-7171.
96. Salvesen, G. S., and Duckett, C. S. (2002). IAP proteins: Blocking the road to death's door. Nat Rev Mol Cell Biol 3, 401-410.
97. Sattler, M., Liang, H., Nettesheim, D., Meadows, R. P., Harlan, J. E, Eberstadt, M., Yoon, H. S, Shuker, S. B., Chang, B. S, and Minn, A. J., et al. (1997). Structure of Bcl-xL-Bak peptide complex: Recognition between regulators of apoptosis. Science 275, 983-986.
98. Schmitz, A. A. P., Govek, E. E., Böttner, B., and Aelst, L. Van (2000). Rho GTPases: Signaling, migration, and invasion Exp. Cell Res. 261(1), 1-12.
99. Sebti, S. M., and Hamilton, A. D. (1997). Inhibition of Ras prenylation: A novel approach to cancer chemotherapy. Pharmacol Ther 74, 103-114.
100. Shacham, S., Topf, M., et al. (2001). Modeling the 3D structure of GPCRs from sequence. Med Res Rev 21(5), 472-483.
101. Shacham, S., Marantz, Y., et al. (2004). PREDICT modeling and in-silico screening for G-protein coupled receptors. Proteins 57(1), 51-86.
102. Shangary, S., and Johnson D. E. (2003). Recent advances in the development of anticancer agents targeting cell death inhibitors in the Bcl-2 protein family. Leukemia 17, 1470-1481.
103. Shawver, L. K., Slamon, D., et al. (2002). Smart drugs: Tyrosine kinase inhibitors in cancer therapy. Cancer Cell 1, 117-123.
104. Shenai, B. R., Lee, B. J., Alvarez-Hernandez, A., Chong, P. Y., Emal, C. D., Neitz, R. J., Roush,W. R., and Rosenthal, P. J. (2003). Structure-activity relationships for inhibition of cysteine protease activity and development of Plasmodium falciparum by peptidyl vinyl sulfones. Antimicrob Agents Chemother 47, 154-160.
105. Song, H.,Wang, R.,Wang, S., and Lin, J. (2005). A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. Proc Natl Acad Sci USA 102(13), 4700-4705.
106. Srinivasula, S. M., Hegde, R., Saleh, A., Datta, P., Shiozaki, E., Chai, J., Lee, R. A., Robbins, P. D., Fernandes-Alnemri, T., Shi, Y., et al. (2001). A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410, 112-116.
107. Stamos, J., Sliwkowski, M. X., et al. (2002). Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol Chem 2777, 46265-46272.
108. Steindl, T. M., Crump, C. E., Hayden, F. G., and Langer, T. (2005). Pharmacophore modeling, docking, and principal component analysis based clustering: Combined computer-assisted approaches to identify new inhibitors of the human rhinovirus coat protein. J Med Chem 48, 6250-6260.
109. Tao, P., and Lai, L. (2001). Protein ligand docking based on empirical method for binding affinity estimation. J Comput Aided Mol Des 15(5), 429-446.
110. Thoma, R., Loffler, B., Stihle, M., Huber,W., Ruf, A., and Hennig, M. (2003). Crystal structure of human dipeptidyl Peptidase IV (DPPIV). Structure 1, 947-959.
111. Tokumaru, S., Higashiyama, S., et al. (2000). Ectodomain shedding of epidermal growth factor receptor ligands is required for keratinocyte migration in cutaneous wound healing. J Cell Biol 151, 209.
112. Totrov, M., and Abagyan, R. (1997). Flexible protein-ligand docking by global energy optimization in internal coordinates. Proteins Suppl 1, 215-220.
113. Totrov, M. and Abagyan, R. A. (2001). Drug-Receptor Thermodynamics: Introduction and Experimental Applications. New York: John Wiley & Sons.
114. Verdonk, M. L., Cole, J. C., Hartshorn, M. J., Murray, C.W., and Taylor, R. D. (2003). Improved protein-ligand docking using GOLD. Proteins 52(4), 609-623.
115. Wallis, R. M., Corbin, J. D., Francis, S. H., and Ellis, P. (1999). Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 83, 3C.
116. Wang, J. L., Liu, D., Zhang, Z. J., Shan, S., Han, X., Srinivasula, S. M., Croce, C. M., Alnemri, E. S., and Huang, Z. (2000). Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci USA 97, 7124-7129.
117. Wang, R., Lu, Y., and Wang, S. (2003). Comparative evaluation of 11 scoring functions for molecular docking. J Med Chem 46(12), 2287-2303.
118. Ward, R. A., Perkins, T. D. J., and Stafford, J. (2005). Structure-based virtual screening for low molecular weight chemical starting points for dipeptidyl peptidase IV inhibitors. J Med Chem 48, 6991-6996.
119. Westbrook, J., Feng, Z., Chen, L., Yang, H., and Berman, H. M. (2003). The Protein Data Bank and structural genomics. Nucleic Acids Res 31, 489-491.
120. Yabe-Nishimura, C. (1998). Aldose reductase in glucose toxicity: A potential target for the prevention of diabetic complications. Pharmacol Rev 50, 21-33.
121. Yamazaki K., K., N., Fujita, K., Sato, H., Asano, S., Dan, A., and Kanaoka, M. (2005). Identification of phosphodiesterase-1 and 5 dual inhibitors by a ligand-based virtual screening optimized for lead evolution. Bioorg Med Chem Lett xxx, xxxx.
122. Yin, X. M., Oltvai, Z. N., et al. (1994). BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 369, 272-273.
123. Zhao, L., and Brinton, R. D. (2005). Structure-based virtual screening for plant-based ERbeta-selective ligands as potential preventative therapy against age-related neurodegenerative diseases. J Med Chem 48(10), 3463-3466.
124. Zheng, Y. (2001). Dbl family guanine nucleotide exchange factors. Trends Biochem Sci 26(12), 724-732.
125. Zhong, Z., Z. Wen, et al. (1994). Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264, 95-98.
126. Zhou, B. B., and Elledge, S. J. (2000). The DNA damage response: Putting checkpoints in perspective. Nature 408(6811): 433-439.