Diverse, high-quality test set for the validation of protein-ligand docking performance

Journal of Medicinal Chemistry

Volumn 50, Issue 4, 2007, Pages 726-741

  Hartshorn, Michael J ^a   Verdonk, Marcel L ^a   Chessari, Gianni ^a   Brewerton, Suzanne C ^a   Mooij, Wijnand T M ^a   Mortenson, Paul N ^a   Murray, Christopher W ^a  

^a ASTEX PHARMACEUTICALS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND; PROTEIN;

AMINO ACID SEQUENCE; ARTICLE; COMPLEX FORMATION; COMPUTER PROGRAM; CRYSTAL STRUCTURE; LIGAND BINDING; MOLECULAR DOCKING; PROTEIN BINDING; STRUCTURE ANALYSIS; VALIDATION PROCESS;

BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DATABASES, PROTEIN; LIGANDS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN BINDING; PROTEINS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; SEQUENCE ANALYSIS, PROTEIN;

EID: 33847347192     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm061277y     Document Type: Article

References (138)

1. Kitchen, D. B.; Decornez, H.; Furr, J. R.; Bajorath, J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat. Rev. Drug Discovery 2004, 3, 935-949.
2. Shoichet, B. K. Virtual screening of chemical libraries. Nature 2004, 432, 862-865.
3. Cole, J. C.; Murray, C. W.; Nissink, J. W.; Taylor, R. D.; Taylor, R. Comparing protein-ligand docking programs is difficult. Proteins 2005, 60, 325-332.
4. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
5. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.
6. Kramer, B.; Rarey, M.; Lengauer, T. Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking. Proteins 1999, 37, 228-241.
7. Pang, Y. P.; Perola, E.; Xu, K.; Prendergast, F. G. EUDOC: a computer program for identification of drug interaction sites in macromolecules and drug leads from chemical databases. J. Comput. Chem. 2001, 22, 1750-1771.
8. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 2004, 47, 1739-1749.
9. Eldridge, M. D.; Murray, C. W.; Auton, T. R.; Paolini, G. V.; Mee, R. P. Empirical scoring functions. 1. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J. Comput.-Aided Mol. Des. 1997, 11, 425-445.
10. Chen, H.; Lyne, P. D.; Giordanetto, F.; Lovell, T.; Li, J. On evaluating molecular-docking methods for pose prediction and enrichment factors. J. Chem. Inf. Model. 2006, 46, 401-415.
11. Paul, N.; Rognan, D. ConsDock: A new program for the consensus analysis of protein-ligand interactions. Proteins 2002, 47, 521-533.
12. Nissink, J. W. M.; Murray, C. W.; Hartshorn, M. J.; Verdonk, M. L.; Cole, J. C.; Taylor, R. A new test set for validating predictions of protein-ligand interaction. Proteins 2002, 49, 457-471.
13. Perola, E.; Walters, W. P.; Charifson, P. S. A detailed comparison of current docking and scoring methods on systems of pharmaceutical relevance. Proteins 2004, 56, 235-249.
14. 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. Nucleic Acids Res. 1997, 25, 3389-3402.
15. Hendlich, M.; Bergner, A.; Gunther, J.; Klebe, G. Relibase: design and development of a database for comprehensive analysis of protein-ligand interactions. J. Mol. Biol. 2003, 326, 607-620.
16. Sayle, R. PDB: Cruft to content (Perception of molecular connectivity from 3D coordinates); Daylight user meeting MUG01, 2001 (http://www.daylight. com/meetings/mug01/Sayle/m4xbondage.html).
17. Wang, R.; Fang, X.; Lu, Y.; Wang, S. The PDBbind database: collection of binding affinities for protein-ligand complexes with known three-dimensional structures. J. Med. Chem. 2004, 47, 2977-2980.
18. Wang, R.; Fang, X.; Lu, Y.; Yang, C. Y.; Wang, S. The PDBbind database: methodologies and updates. J. Med. Chem. 2005, 48, 4111-4119.
19. Elsevier MDL, 2440 Camino Ramon, Suite 300, San Ramon, CA 94583, 2006.
20. Weininger, D. SMILES a chemical language and information system. 1. Introduction to methodology and encoding rules. J. Chem. Inf. Comput. Sci. 1998, 28, 31-36.
21. Daylight Chemical Information Systems, Inc., Aliso Vieja, CA; www.daylight.com, 2006.
22. BioByte Corp. 201 W. 4th St., #204, Claremont, CA 9171 1-4707, 2006.
23. Tsai, J.; Taylor, R.; Chothia, C.; Gerstein, M. The packing density in proteins: standard radii and volumes. J. Mol. Biol. 1999, 290, 253-266.
24. Mooij, W. T.; Hartshorn, M. J.; Tickle, I. J.; Sharff, A. J.; Verdonk, M. L.; Jhoti, H. Automated protein-ligand crystallography for structure-based drug design. ChemMedChem 2006, 1, 827-838.
25. Hartshorn, M. J.; Murray, C. W.; Cleasby, A.; Frederickson, M.; Tickle, I. J.; Jhoti, H. Fragment-based lead discovery using X-ray crystallography. J. Med. Chem. 2005, 48, 403-413.
26. Kleywegt, G. J.; Harris, M. R.; Zou, J. Y.; Taylor, T. C.; Wahlby, A.; Jones, T. A. The Uppsala Electron-Density Server. Acta Crystallogr., Sect. D 2004, 60, 2240-2249.
27. Gasteiger, J.; Rudolph, C.; Sadowski, J. Automatic generation of 3D-atomic coordinates for organic molecules. Tetrahedron Comput. Methodol. 1990, 3, 537-547.
28. Hartshorn, M. J. AstexViewer: a visualisation aid for structure-based drug design. J. Comput.-Aided Mol. Des. 2002, 16, 871-881.
29. Allen, F. H. The Cambridge Structural Database: a quarter of a million crystal structures and rising. Acta Crystallogr., Sect. B 2002, 58, 380-388.
30. Accelrys, Inc., Insightll, San Diego: Accelrys, Inc., 2005.
31. Halgren, T. A. The representation of van der Waals (vdW) interactions in molecular mechanics force fields: potential form, combination rules and vdW parameters. J. Am. Chem. Soc. 1992, 114, 7827-7843.
32. Taylor, R. D.; Jewsbury, P. J.; Essex, J. W. A review of protein-small molecule docking methods. J. Comput.-Aided Mol. Des. 2002, 16, 151-166.
33. Verdonk, M. L.; Cole, J. C.; Hartshorn, M.; Murray, C. W.; Taylor, R. D. Improved protein-ligand docking using GOLD. Proteins 2003, 52, 609-623.
34. Kirton, S. B.; Murray, C. W.; Verdonk, M. L.; Taylor, R. D. Prediction of binding modes for ligands in the cytochromes P450 and other heme-containing proteins. Proteins 2005, 58, 836-844.
35. Rarey, M.; Kramer, B.; Lengauer, T. The particle concept: Placing discrete water molecules during protein-ligand docking predictions. Proteins 1999, 34, 17-28.
36. Verdonk, M. L.; Chessari, G.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Nissink, J. W.; Taylor, R. D.; Taylor, R. Modeling water molecules in protein-ligand docking using GOLD. J. Med. Chem. 2005, 48, 6504-6515.
37. Goto, J.; Kataoka, R.; Hirayama, N. Ph4Dock: pharmacophore-based protein-ligand docking. J. Med. Chem. 2004, 47, 6804-6811.
38. De Graaf, C.; Pospisil, P.; Pos, W.; Folkers, G.; Vermeulen, N. P. E. Binding mode prediction of cytochrome P450 and thymidine kinase protein-ligand complexes by consideration of water and rescoring in automated docking. J. Med. Chem. 2005, 48, 2308-2318.
39. Erickson, J. A.; Jalaie, M.; Robertson, D. H.; Lewis, R. A.; Vieth, M. Lessons in molecular recognition: the effects of ligand and protein flexibility on molecular docking accuracy. J. Med. Chem. 2004, 47, 45-55.
40. Glen, R. C.; Payne, A. W. A genetic algorithm for the automated generation of molecules within constraints. J. Comput.-Aided Mol. Des. 1995, 9, 181-202.
41. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliver Rev. 1997, 23, 3-25.
42. Safo, M. K.; Moure, C. M.; Burnett, J. C.; Joshi, G. S.; Abraham, D. J. High-resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector. Protein Sci. 2001, 10, 951-957.
43. Rowsell, S.; Hawtin, P.; Minshull, C. A.; Jepson, H.; Brockbank, S. M.; Barratt, D. G.; Slater, A. M.; McPheat, W. L.; Waterson, D.; Henney, A. M.; Pauptit, R. A. Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor. J. Mol. Biol. 2002, 319, 173-181.
44. McVey, C. E.; Walsh, M. A.; Dodson, G. G.; Wilson, K. S.; Brannigan, J. A. Crystal structures of penicillin acylase enzyme-substrate complexes: structural insights into the catalytic mechanism. J. Mol. Biol. 2001, 313, 139-150.
45. Dvir, H.; Jiang, H. L.; Wong, D. M.; Harel, M.; Chetrit, M.; He, X. C.; Jin, G. Y.; Yu, G. L.; Tang, X. C.; Silman, I.; Bai, D. L.; Sussman, J. L. X-ray structures of Torpedo californica acetylcholinesterase complexed with (+)-huperzine A and (-)-huperzine B: structural evidence for an active site rearrangement. Biochemistry 2002, 41, 10810-10818.
46. Martin, J. L.; Begun, J.; McLeish, M. J.; Caine, J. M.; Grunewald, G. L. Getting the adrenaline going: crystal structure of the adrenaline-synthesizing enzyme PNMT. Structure 2001, 9, 977-985.
47. Versees, W.; Decanniere, K.; Pelle, R.; Depoorter, J.; Brosens, E.; Parkin, D. W.; Steyaert, J. Structure and function of a novel purine specific nucleoside hydrolase from Trypanosoma vivax. J. Mol. Biol. 2001, 307, 1363-1379.
48. Blaszczyk, J.; Li, Y.; Shi, G.; Yan, H.; Ji, X. Dynamic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: crystallographic studies. Biochemistry 2003, 42, 1573-1580.
49. Li, Y.; Blaszczyk, J.; Wu, Y.; Shi, G.; Ji, X.; Yan, H. Is the critical role of loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase in catalysis due to loop-3 residues arginine-84 and tryptophan-89? Site-directed mutagenesis, biochemical, and crystallographic studies. Biochemists 2005, 44, 8590-8599.
50. Phan, J.; Koli, S.; Minor, W.; Dunlap, R. B.; Berger, S. H.; Lebioda, L. Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry 2001, 40, 1897-1902.
51. Rutenber, E. E.; Stroud, R. M. Binding of the anticancer drug ZD1694 to E. coli thymidylate synthase: assessing specificity and affinity. Structure 1996, 4, 1317-1324.
52. Istvan, E. S.; Deisenhofer, J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 2001, 292, 1160-1164.
53. van den Elsen, J. M.; Kuntz, D. A.; Rose, D. R. Structure of Golgi alpha-mannosidase II: a target for inhibition of growth and metastasis of cancer cells. EMBO J. 2001, 20, 3008-3017.
54. Whitlow, M.; Howard, A. J.; Stewart, D.; Hardman, K. D.; Chan, J. H.; Baccanari, D. P.; Tansik, R. L.; Hong, J. S.; Kuyper, L. F. X-ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor. J. Med. Chem. 2001, 44, 2928-2932.
55. Timm, D. E.; Liu, J.; Baker, L. J.; Harris, R. A. Crystal structure of thiamin pyrophosphokinase. J. Mol. Biol. 2001, 310, 195-204.
56. Yuvaniyama, J.; Chitnumsub, P.; Kamchonwongpaisan, S.; Vanichtanankul, J.; Sirawaraporn, W.; Taylor, P.; Walkinshaw, M. D.; Yuthavong, Y. Insights into antifolate resistance from malarial DHFRTS structures. Nat. Struct. Biol. 2003, 10, 357-365.
57. Vullo, D.; Innocenti, A.; Nishimori, I.; Pastorek, J.; Scozzafava, A.; Pastorekova, S.; 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? Bioorg. Med. Chem. Lett. 2005, 15, 963-969.
58. Whittington, D. A.; Waheed, A.; Ulmasov, B.; Shah, G. N.; Grubb, J. H.; Sly, W. S.; Christianson, D. W. Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 9545-9550.
59. Toney, J. H.; Hammond, G. G.; Fitzgerald, P. M.; Sharma, N.; Balkovec, J. M.; Rouen, G. P.; Olson, S. H.; Hammond, M. L.; Greenlee, M. L.; Gao, Y. D. Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta- lactamase. J. Biol. Chem. 2001, 276, 31913-31918.
60. Ren, J.; Nichols, C.; Bird, L.; Chamberlain, P.; Weaver, K.; Short, S.; Stuart, D. I.; Stammers, D. K. Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors. J. Mol. Biol. 2001, 312, 795-805.
61. Weyand, M.; Schlichting, I.; Marabotti, A.; Mozzarelli, A. Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase. J. Biol. Chem. 2002, 277, 10647-10652.
62. Bramson, H. N.; Corona, J.; Davis, S. T.; Dickerson, S. H.; Edelstein, M.; Frye, S. V.; Gampe, R. T., Jr.; Harris, P. A.; Hassell, A.; Holmes, W. D.; Hunter, R. N.; Lackey, K. E.; Lovejoy, B.; Luzzio, M. J.; Montana, V.; Rocque, W. J.; Rusnak, D.; Shewchuk, L.; Veal, J. M.; Walker, D. H.; Kuyper, L. F. Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis. J. Med. Chem. 2001, 44, 4339-4358.
63. Reiling, K. K.; Endres, N. F.; Dauber, D. S.; Craik, C. S.; Stroud, R. M. Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and thermodynamic binding mode examined in a 1.09 Å structure. Biochemistry 2002, 41, 4582-4594.
64. Powers, R. A.; Morandi, F.; Shoichet, B. K. Structure-based discovery of a novel, noncovalent inhibitor of AmpC beta-lactamase. Structure 2002, 10, 1013-1023.
65. Babu, Y. S.; Chand, P.; Bantia, S.; Kotian, P.; Dehghani, A.; El Kattan, Y.; Lin, T. H.; Hutchison, T. L.; Elliott, A. J.; Parker, C. D.; Ananth, S. L.; Horn, L. L.; Laver, G. W.; Montgomery, J. A. BCX-1812 (RWJ-270201): discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design. J. Med. Chem. 2000, 43, 3482-3486.
66. Smith, B. J.; McKimm-Breshkin, J. L.; McDonald, M.; Fernley, R. T.; Varghese, J. N.; Colman, P. M. Structural studies of the resistance of influenza virus neuramindase to inhibitors. J. Med. Chem. 2002, 45, 2207-2212.
67. Matter, H.; Defossa, E.; Heinelt, U.; Blohm, P. M.; Schneider, D.; Muller, A.; Herok, S.; Schreuder, H.; Liesum, A.; Brachvogel, V.; Lonze, P.; Walser, A.; Al Obeidi, F.; Wildgoose, P. Design and quantitative structure-activity relationship of 3-amidinobenzyl-1H-indole-2-carboxamides as potent, nonchiral, and selective inhibitors of blood coagulation factor Xa. J. Med. Chem. 2002, 45, 2749-2769.
68. Woo, E. J.; Marshall, J.; Bauly, J.; Chen, J. G.; Venis, M.; Napier, R. M.; Pickersgill, R. W. Crystal structure of auxin-binding protein 1 in complex with auxin. EMBO J. 2002, 21, 2877-2885.
69. Bledsoe, R. K.; Montana, V. G.; Stanley, T. B.; Delves, C. J.; Apolito, C. J.; McKee, D. D.; Consler, T. G.; Parks, D. J.; Stewart, E. L.; Willson, T. M.; Lambert, M. H.; Moore, J. T.; Pearce, K. H.; Xu, H. E. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 2002, 110, 93-105.
70. Prosise, G. L.; Luecke, H. Crystal structures of Tritrichomonasfoetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism. J. Mol. Biol. 2003, 326, 517-527.
71. Bretscher, L. E.; Li, H.; Poulos, T. L.; Griffith, O. W. Structural characterization and kinetics of nitric-oxide synthase inhibition by novel N5-(iminoalkyl)- and N5-(iminoalkenyl)-ornithines. J. Biol. Chem. 2003, 278, 46789-46797.
72. deSolms, S. J.; Ciccarone, T. M.; MacTough, S. C.; Shaw, A. W.; Buser, C. A.; Ellis-Hutchings, M.; Fernandes, C.; Hamilton, K. A.; Huber, H. E.; Kohl, N. E.; Lobell, R. B.; Robinson, R. G.; Tsou, N. N.; Walsh, E. S.; Graham, S. L.; Beese, L. S.; Taylor, J. S. Dual protein farnesyltransferase- geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents. J. Med. Chem. 2003, 46, 2973-2984.
73. Rasmussen, H. B.; Branner, S.; Wiberg, F. C.; Wagtmann, N. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog. Nat. Struct. Biol. 2003, 10, 19-25.
74. Wang, S.; Eisenberg, D. Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate. Protein Sci. 2003, 12, 1097-1108.
75. Brenk, R.; Naerum, L.; Gradler, U.; Gerber, H. D.; Garcia, G. A.; Reuter, K.; Stubbs, M. T.; Klebe, G. Virtual screening for submicromolar leads of tRNA-guanine transglycosylase based on a new unexpected binding mode detected by crystal structure analysis. J. Med. Chem. 2003, 46, 1133-1143.
76. Dow, R. L.; Schneider, S. R.; Paight, E. S.; Hank, R. F.; Chiang, P.; Cornelius, P.; Lee, E.; Newsome, W. P.; Swick, A. G.; Spitzer, J.; Hargrove, D. M.; Patterson, T. A.; Pandit, J.; Chrunyk, B. A.; LeMotte, P. K.; Danley, D. E.; Rosner, M. H.; Ammirati, M. J.; Simons, S. P.; Schulte, G. K.; Tate, B. F.; DaSilva-Jardine, P. Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands: potent. TR beta subtype-selective thyromimetics. Bioorg. Med. Chem. Lett. 2003, 13, 379-382.
77. Ye, L.; Li, Y. L.; Mellstrom, K.; Mellin, C.; Bladh, L. G.; Koehler, K.; Garg, N.; Garcia Collazo, A. M.; Litten, C.; Husman, B.; Persson, K.; Ljunggren, J.; Grover, G.; Sleph, P. G.; George, R.; Malm, J. Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1. J. Med. Chem. 2003, 46, 1580-1588.
78. Schelling, P.; Claus, M. T.; Johner, R.; Marquez, V. E.; Schulz, G. E.; Scapozza, L. Biochemical and structural characterization of (South)- methanocarbathymidine that specifically inhibits growth of herpes simplex virus type 1 thymidine kinase-transduced osteosarcoma cells. J. Biol. Chem. 2004, 279, 32832-32838.
79. Hartmann, M.; Schneider, T. R.; Pfeil, A.; Heinrich, G.; Lipscomb, W. N.; Braus, G. H. Evolution of feedback-inhibited beta/alpha barrel isoenzymes by gene duplication and a single mutation. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 862-867.
80. Nagar, B.; Hantschel, O.; Young, M. A.; Scheffzek, K.; Veach, D.; Bornmann, W.; Clarkson, B.; Superti-Furga, G.; Kuriyan, J. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 2003, 112, 859-871.
81. Weber, A.; Casini, A.; Heine, A.; Kuhn, D.; Supuran, C. T.; Scozzafava, A.; Klebe, G. Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition. J. Med. Chem 2004, 47, 550-557.
82. Wendt, M. D.; Rockway, T. W.; Geyer, A.; McClellan, W.; Weitzberg, M.; Zhao, X.; Mantei, R.; Nienaber, V. L.; Stewart, K.; Klinghofer, V.; Giranda, V. L. Identification of novel binding interactions in the development of potent, selective 2-naphthamidine inhibitors of urokinase. Synthesis, structural analysis, and SAR of N-phenyl amide 6-substitution. J. Med. Chem. 2004, 47, 303-324.
83. Olsen, J. A.; Banner, D. W.; Seiler, P.; Obst, S. U.; D'Arcy, A.; Stihle, M.; Muller, K.; Diederich, F. A fluorine scan of thrombin inhibitors to map the fluorophilicity/fluorophobicity of an enzyme active site: evidence for C-F⋯C=O interactions. Angew. Chem., Int. Ed. 2003, 42, 2507-2511.
84. Strickler, M.; Goldstein, B. M.; Maxfield, K.; Shireman, L.; Kim, G.; Matteson, D. S.; Jones, J. P. Crystallographic studies on the complex behavior of nicotine binding to P450cam (CYP101). Biochemistry 2003, 42, 11943-11950.
85. Sabini, E.; Ort, S.; Monnerjahn, C.; Konrad, M.; Lavie, A. Structure of human dCK suggests strategies to improve anticancer and antiviral therapy. Nat. Struct. Biol. 2003, 10, 513-519.
86. Scapin, G.; Patel, S. B.; Lisnock, J.; Becker, J. W.; LoGrasso, P. V. The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity. Chem. Biol. 2003, 10, 705-712.
87. Shi, W.; Ting, L. M.; Kicska, G. A.; Lewandowicz, A.; Tyler, P. C.; Evans, G. B.; Furneaux, R. H.; Kim, K.; Almo, S. C.; Schramm, V. L. Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function. J. Biol. Chem. 2004, 279, 18103-18106.
88. Bertrand, J. A.; Thieffine, S.; Vulpetti, A.; Cristiani, C.; Valsasina, B.; Knapp, S.; Kalisz, H. M.; Flocco, M. Structural characterization of the GSK-3beta active site using selective and nonselective ATP-mimetic inhibitors. J. Mol. Biol. 2003, 333, 393-407.
89. Gupta, K.; Kaub, C. J.; Carey, K. N.; Casillas, E. G.; Selinsky, B. S.; Loll, P. J. Manipulation of kinetic profiles in 2-aryl propionic acid cyclooxygenase inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 667-671.
90. Gupta, K.; Selinsky, B. S.; Kaub, C. J.; Katz, A. K.; Loll, P. J. The 2.0 Å resolution crystal structure of prostaglandin H2 synthase-1: structural insights into an unusual peroxidase. J. Mol. Biol. 2004, 335, 503-518.
91. Chen, H.; Noble, F.; Mothe, A.; Meudal, H.; Coric, P.; Danascimento, S.; Roques, B. P.; George, P.; Fournie-Zaluski, M. C. Phosphinic derivatives as new dual enkephalin-degrading enzyme inhibitors: synthesis, biological properties, and antinociceptive activities. J. Med. Chem. 2000, 43, 1398-1408.
92. Oefner, C.; Roques, B. P.; Fournie-Zaluski, M. C.; Dale, G. E. Structural analysis of neprilysin with various specific and potent inhibitors. Acta Crystallogr., Sect. D 2004, 60, 392-396.
93. Orth, P.; Reichert, P.; Wang, W.; Prosise, W. W.; Yarosh-Tomaine, T.; Hammond, G.; Ingram, R. N.; Xiao, L.; Mirza, U. A.; Zou, J.; Strickland, C.; Taremi, S. S.; Le, H. V.; Madison, V. Crystal structure of the catalytic domain of human ADAM33. J. Mol. Biol. 2004, 335, 129-137.
94. Zou, J.; Zhu, F.; Liu, J.; Wang, W.; Zhang, R.; Garlisi, C. G.; Liu, Y. H.; Wang, S.; Shah, H.; Wan, Y.; Umland, S. P. Catalytic activity of human ADAM33. J. Biol. Chem. 2004, 279, 9818-9830.
95. Sheppard, G. S.; Wang, J.; Kawai, M.; BaMaung, N. Y.; Craig, R. A.; Erickson, S. A.; Lynch, L.; Patel, J.; Yang, F.; Searle, X. B.; Lou, P.; Park, C.; Kim, K. H.; Henkin, J.; Lesniewski, R. 3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2. Bioorg. Med. Chem Lett. 2004, 14, 865-868.
96. Wester, M. R.; Yano, J. K.; Schoch, G. A.; Yang, C.; Griffin, K. J.; Stout, C. D.; Johnson, E. F. The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0 Å resolution. J. Biol. Chem. 2004, 279, 35630-35637.
97. Tocchini-Valentini, G.; Rochel, N.; Wurtz, J. M.; Moras, D. Crystal structures of the vitamin D nuclear receptor liganded with the vitamin D side chain analogues calcipotriol and seocalcitol, receptor agonists of clinical importance. Insights into a structural basis for the switching of calcipotriol to a receptor antagonist by further side chain modification. J. Med. Chem. 2004, 47, 1956-1961.
98. Cody, V.; Luft, J. R.; Pangborn, W.; Gangjee, A.; Queener, S. F. Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry. Acta Crystallogr., Sect. D 2004, 60, 646-655.
99. Gangjee, A.; Zaveri, N.; Kothare, M.; Queener, S. F. Nonclassical 2,4-diamino-6-(aminomethyl)-5,6,7,8-tetrahydroquinazoline antifolates: synthesis and biological activities. J. Med. Chem. 1995, 38, 3660-3668.
100. Buryanovskyy, L.; Fu, Y.; Boyd, M.; Ma, Y.; Hsieh, T. C.; Wu, J. M.; Zhang, Z. Crystal structure of quinone reductase 2 in complex with resveratrol. Biochemistry 2004, 43, 11417-11426.
101. Kim, S.; Wu, J. Y.; Birzin, E. T.; Frisch, K.; Chan, W.; Pai, L. Y.; Yang, Y. T.; Mosley, R. T.; Fitzgerald, P. M.; Sharma, N.; Dahllund, J.; Thorsell, A. G.; DiNinno, F.; Rohrer, S. P.; Schaeffer, J. M.; Hammond, M. L. Estrogen receptor ligands. II. Discovery of benzoxathiins as potent, selective estrogen receptor alpha modulators. J. Med. Chem. 2004, 47, 2171-2175.
102. Ivey, R. A.; Zhang, Y. M.; Virga, K. G.; Hevener, K.; Lee, R. E.; Rock, C. O.; Jackowski, S.; Park, H. W. The structure of the pantothenate kinase-ADP-pantothenate ternary complex reveals the relationship between the binding sites for substrate, allosteric regulator, and antimetabolites. J. Biol. Chem. 2004, 279, 35622-35629.
103. Song, W. J.; Jackowski, S. Kinetics and regulation of pantothenate kinase from Escherichia coli. J. Biol. Chem. 1994, 269, 27051-27058.
104. Madauss, K. P.; Deng, S. J.; Austin, R. J.; Lambert, M. H.; McLay, I.; Pritchard, J.; Short, S. A.; Stewart, E. L.; Uings, I. J.; Williams, S. P. Progesterone receptor ligand binding pocket flexibility: crystal structures of the norethindrone and mometasone furoate complexes. J. Med. Chem. 2004, 47, 3381-3387.
105. Ruiz, F.; Hazemann, I.; Mitschler, A.; Joachimiak, A.; Schneider, T.; Karplus, M.; Podjarny, A. The crystallographic structure of the aldose reductase-IDD552 complex shows direct proton donation from tyrosine 48. Acta Crystallogr., Sect. D 2004, 60, 1347-1354.
106. Manley, P. W.; Cowan-Jacob, S. W.; Buchdunger, E.; Fabbro, D.; Fendrich, G.; Furet, P.; Meyer, T.; Zimmermann, J. Imatinib: a selective tyrosine kinase inhibitor. Eur. J. Cancer 2002, 38 (Suppl 5), S19-S27.
107. Mol, C. D.; Dougan, D. R.; Schneider, T. R.; Skene, R. J.; Kraus, M. L.; Scheibe, D. N.; Snell, G. P.; Zou, H.; Sang, B. C.; Wilson, K. P. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J. Biol. Chem. 2004, 279, 31655-31663.
108. Duggleby, R. G.; Pang, S. S.; Yu, H.; Guddat, L. W. Systematic characterization of mutations in yeast acetohydroxyacid synthase. Interpretation of herbicide-resistance data. Eur. J. Biochem. 2003, 270, 2895-2904.
109. McCourt, J. A.; Pang, S. S.; Guddat, L. W.; Duggleby, R. G. Elucidating the specificity of binding of sulfonylurea herbicides to acetohydroxyacid synthase. Biochemistry 2005, 44, 2330-2338.
110. Lehmann, F.; Haile, S.; Axen, E.; Medina, C.; Uppenberg, J.; Svensson, S.; Lundback, T.; Rondahl, L.; Barf, T. Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target. Bioorg. Med. Chem. Lett. 2004, 14, 4445-4448.
111. Mayer, M. L. Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron 2005, 45, 539-552.
112. Morais-de-Sa, E.; Pereira, P. J.; Saraiva, M. J.; Damas, A. M. The crystal structure of transthyretin in complex with diethylstilbestrol: a promising template for the design of amyloid inhibitors. J. Biol. Chem. 2004, 279, 53483-53490.
113. Bu, W.; Settembre, E. C.; el Kouni, M. H.; Ealick, S. E. Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines. Acta Crystallogr., Sect. D 2005, 61, 863-872.
114. Steinbacher, S.; Kaiser, J.; Wungsintaweekul, J.; Hecht, S.; Eisenreich, W.; Gerhardt, S.; Bacher, A.; Rohdich, F. Structure of 2C-methyl-D-erythritol-2, 4-cyclodiphosphate synthase involved in mevalonate-independent biosynthesis of isoprenoids. J. Mol. Biol. 2002, 316, 79-88.
115. Terasaka, T.; Kinoshita, T.; Kuno, M.; Seki, N.; Tanaka, K.; Nakanishi, I. Structure-based design, synthesis, and structure-activity relationship studies of novel non-nucleoside adenosine deaminase inhibitors. J. Med. Chem. 2004, 47, 3730-3743.
116. Mapelli, M.; Massimiliano, L.; Crovace, C.; Seeliger, M. A.; Tsai, L. H.; Meijer, L.; Musacchio, A. Mechanism of CDK5/p25 binding by CDK inhibitors. J. Med. Chem. 2005, 48, 671-679.
117. Cole, C.; Reigan, P.; Gbaj, A.; Edwards, P. N.; Douglas, K. T.; Stratford, I. J.; Freeman, S.; Jaffar, M. Potential tumor-selective nitroimidazolylmethyluracil prodrug derivatives: inhibitors of the angiogenic enzyme thymidine phosphorylase. J. Med. Chem. 2003, 46, 207-209.
118. Norman, R. A.; Barry, S. T.; Bate, M.; Breed, J.; Colls, J. G.; Ernill, R. J.; Luke, R. W.; Minshull, C. A.; McAlister, M. S.; McCall, E. J.; McMiken, H. H.; Paterson, D. S.; Timms, D.; Tucker, J. A.; Pauptit, R. A. Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor. Structure 2004, 12, 75-84.
119. Holton, S.; Merckx, A.; Burgess, D.; Doerig, C.; Noble, M.; Endicott, J. Structures of P. falciparum PfPK5 test the CDK regulation paradigm and suggest mechanisms of small molecule inhibition. Structure 2003, 11, 1329-1337.
120. Le Roch, K.; Sestier, C.; Dorin, D.; Waters, N.; Kappes, B.; Chakrabarti, D.; Meijer, L.; Doerig, C. Activation of a Plasmodium falciparum cdc2-related kinase by heterologous p25 and cyclin H. Functional characterization of a P. falciparum cyclin homologue. J. Biol. Chem. 2000, 275, 8952-8958.
121. Luic, M.; Koellner, G.; Yokomatsu, T.; Shibuya, S.; Bzowska, A. Calf spleen purine-nucleoside phosphorylase: crystal structure of the binary complex with a potent multisubstrate analogue inhibitor. Acta Crystallogr., Sect. D 2004, 60, 1417-1424.
122. Kamata, K.; Mitsuya, M.; Nishimura, T.; Eiki, J.; Nagata, Y. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase. Structure 2004, 12, 429-438.
123. Lommer, B. S.; Ali, S. M.; Bajpai, S. N.; Brouillette, W. J.; Air, G. M.; Luo, M. A benzoic acid inhibitor induces a novel conformational change in the active site of Influenza B virus neuraminidase. Acta Crystallogr., Sect. D 2004, 60, 1017-1023.
124. Houston, D. R.; Synstad, B.; Eijsink, V. G.; Stark, M. J.; Eggleston, I. M.; van Aalten, D. M. Structure-based exploration of cyclic dipeptide chitinase inhibitors. J. Med. Chem. 2004, 47, 5713-5720.
125. Fioravanti, E.; Adam, V.; Munier-Lehmann, H.; Bourgeois, D. The crystal structure of Mycobacterium tuberculosis thymidylate kinase in complex with 3′-azidodeoxythymidine monophosphate suggests a mechanism for competitive inhibition. Biochemistry 2005, 44, 130-137.
126. Vanheusden, V.; Van Rompaey, P.; Munier-Lehmann, H.; Pochet, S.; Herdewijn, P.; Van Calenbergh, S. Thymidine and thymidine-5′-O- monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase. Bioorg. Med. Chem. Lett. 2003, 13, 3045-3048.
127. Kobayashi, T.; Takimura, T.; Sekine, R.; Kelly, V. P.; Kamata, K.; Sakamoto, K.; Nishimura, S.; Yokoyama, S. Structural snapshots of the KMSKS loop rearrangement for amino acid activation by bacterial tyrosyl-tRNA synthetase. J. Mol. Biol. 2005, 346, 105-117.
128. Card, G. L.; England, B. P.; Suzuki, Y.; Fong, D.; Powell, B.; Lee, B.; Luu, C.; Tabrizizad, M.; Gillette, S.; Ibrahim, P. N.; Artis, D. R.; Bollag, G.; Milburn, M. V.; Kim, S. H.; Schlessinger, J.; Zhang, K. Y. Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure 2004, 12, 2233-2247.
129. Harris, P. A.; Cheung, M.; Hunter, R. N., III; Brown, M. L.; Veal, J. M.; Nolte, R. T.; Wang, L.; Liu, W.; Crosby, R. M.; Johnson, J. H.; Epperly, A. H.; Kumar, R.; Luttrell, D. K.; Stafford, J. A. Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J. Med. Chem. 2005, 48, 1610-1619.
130. Olivero, A. G.; Eigenbrot, C.; Goldsmith, R.; Robarge, K.; Artis, D. R.; Flygare, J.; Rawson, T.; Sutherlin, D. P.; Kadkhodayan, S.; Beresini, M.; Elliott, L. O.; DeGuzman, G. G.; Banner, D. W.; Ultsch, M.; Marzec, U.; Hanson, S. R.; Refino, C.; Bunting, S.; Kirchhofer, D. A selective, slow binding inhibitor of factor VIIa binds to a nonstandard active site conformation and attenuates thrombus formation in vivo. J. Biol. Chem. 2005, 280, 9160-9169.
131. Shoop, W. L.; Xiong, Y.; Wiltsie, J.; Woods, A.; Guo, J.; Pivnichny, J. V.; Felcetto, T.; Michael, B. F.; Bansal, A.; Cummings, R. T.; Cunningham, B. R.; Friedlander, A. M.; Douglas, C. M.; Patel, S. B.; Wisniewski, D.; Scapin, G.; Salowe, S. P.; Zaller, D. M.; Chapman, K. T.; Scolnick, E. M.; Schmatz, D. M.; Bartizal, K.; MacCoss, M.; Hermes, J. D. Anthrax lethal factor inhibition. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 7958-7963.
132. Allingham, J. S.; Smith, R.; Rayment, I. The structural basis of blebbistatin inhibition and specificity for myosin II. Nat. Struct. Mol. Biol. 2005, 12, 378-379.
133. Pfefferkorn, J. A.; Greene, M. L.; Nugent, R. A.; Gross, R. J.; Mitchell, M. A.; Finzel, B. C.; Harris, M. S.; Wells, P. A.; Shelly, J. A.; Anstaut, R. A.; Kilkuskie, R. E.; Kopta, L. A.; Schwende, F. J. Inhibitors of HCV NS5B polymerase. Part 1: Evaluation of the southern region of (2Z)-2-(benzoylamino)- 3-(5-phenyl-2-furyl)acrylic acid. Bioorg. Med. Chem. Lett. 2005, 15, 2481-2486.
134. Golebiowski, A.; Townes, J. A.; Laufersweiler, M. J.; Brugel, T. A.; Clark, M. P.; Clark, C. M.; Djung, J. F.; Laughlin, S. K.; Sabat, M. P.; Bookland, R. G.; VanRens, J. C.; De, B.; Hsieh, L. C.; Janusz, M. J.; Walter, R. L.; Webster, M. E.; Mekel, M. J. The development of monocyclic pyrazolone based cytokine synthesis inhibitors. Bioorg. Med. Chem. Lett. 2005, 15, 2285-2289.
135. Bohl, C. E.; Gao, W.; Miller, D. D.; Bell, C. E.; Dalton, J. T. Structural basis for antagonism and resistance of bicalutamide in prostate cancer. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 6201-6206.
136. Levell, J.; Astles, P.; Eastwood, P.; Cairns, J.; Houille, O.; Aldous, S.; Merriman, G.; Whiteley, B.; Pribish, J.; Czekaj, M.; Liang, G.; Maignan, S.; Guilloteau, J. P.; Dupuy, A.; Davidson, J.; Harrison, T.; Morley, A.; Watson, S.; Fenton, G.; McCarthy, C.; Romano, J.; Mathew, R.; Engers, D.; Gardyan, M.; Sides, K.; Kwong, J.; Tsay, J.; Rebello, S.; Shen, L.; Wang, J.; Luo, Y.; Giardino, O.; Lim, H. K.; Smith, K.; Pauls, H. Structure-based design of 4-(3-aminomethylphenyl)piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of betaII tryptase. Bioorg. Med. Chem. 2005, 13, 2859-2872.
137. Foloppe, N.; Fisher, L. M.; Howes, R.; Kierstan, P.; Potter, A.; Robertson, A. G.; Surgenor, A. E. Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity. J. Med. Chem. 2005, 48, 4332-4345.
138. Dymock, B. W.; Barril, X.; Brough, P. A.; Cansfield, J. E.; Massey, A.; McDonald, E.; Hubbard, R. E.; Surgenor, A.; Roughley, S. D.; Webb, P.; Workman,