HIV-reverse transcriptase inhibition: Inclusion of ligand-induced fit by cross-docking studies

Journal of Medicinal Chemistry

Volumn 48, Issue 1, 2005, Pages 200-212

  Ragno, Rino ^b   Frasca, Simona ^b   Manetti, Fabrizio ^a   Brizzi, Antonella ^a   Massa, Silvio ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF SIENA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1 [(2 HYDROXYETHOXY)METHYL] 6 (PHENYLTHIO)THYMINE; 6 CHLORO 2 [(1 FURO[2,3 C]PYRIDIN 5 YLETHYL)THIO] 4 PYRIMIDINAMINE; 9 CHLORO 4,5,6,7 TETRAHYDRO 5 METHYL 6 (3 METHYL 2 BUTENYL)IMIDAZO[4,5,1 JK][1,4]BENZODIAZEPINE 2(1H) THIONE; CAPRAVIRINE; DELAVIRDINE; EFAVIRENZ; EMIVIRINE; GCA 186; LIGAND; MSC 194; MSC 204; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; NEVIRAPINE; R 90385; R 95845; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; TALVIRALINE; TIVIRAPINE; TNK 6123; TNK 651; UC 10; UC 38; UC 84; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; COMPLEX FORMATION; DRUG BINDING SITE; DRUG DESIGN; DRUG EFFECT; DRUG INHIBITION; DRUG MECHANISM; DRUG STRUCTURE; ENZYME INHIBITION; STRUCTURE ACTIVITY RELATION;

BINDING SITES; DRUG DESIGN; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; LIGANDS; MODELS, MOLECULAR; MUTATION; NUCLEOSIDES; PROTEIN CONFORMATION; REVERSE TRANSCRIPTASE INHIBITORS; SOFTWARE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 12144278681     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0493921     Document Type: Article

References (75)

1. Davey, R. T., Jr.; Dewar, R. L.; Reed, G. F.; Vasudevachari, M. B.; Polis, M. A.; Kovacs, J. A.; Falloon, J.; Walker, R. E.; Masur, H.; et al. Plasma viremia as a sensitive indicator of the antiretroviral activity of L-697661. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 5608-5612.
2. Wallace, R. G. AIDS in the HAART era: New York's heterogeneous geography. Soc. Sci. Med. 2003, 56, 1155-1171.
3. De Clercq, E. The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection. Antiviral Res. 1998, 38, 153-179.
4. Pedersen, O. S.; Pedersen, E. B. Non-nucleoside reverse transcriptase inhibitors: the NNRTI boom. Antiviral Chem. Chemother. 1999, 10, 285-314.
5. Campiani, G.; Ramunno, A.; Maga, G.; Nacci, V.; Fattorusso, C.; Catalanotti, B.; Morelli, E.; Novellino, E. Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: Past, present, and future perspectives. Curr. Pharm. Des. 2002, 8, 615-657.
6. Schaefer, W.; Friebe, W. G.; Leinert, H.; Mertens, A.; Poll, T.; Von der Saal, W.; Zilch, H.; Nuber, B.; Ziegler, M. L. Non-nucleoside inhibitors of HIV-1 reverse transcriptase: molecular modeling and x-ray structure investigations. J. Med. Chem. 1993, 36, 726-732.
7. Lawtrakul, L.; Beyer, A.; Hannongbua, S.; Wolschann, P. Quantitative Structural Rearrangement of HIV-1 Reverse Transcriptase on Binding to Non-Nucleoside Inhibitors. Monatsh. Chem. 2004, 135, 1033-1046.
8. Das, K.; Clark, A. D., Jr.; Lewi, P. J.; Heeres, J.; De Jonge, M. R.; Koymans, L. M. H.; Vinkers, H. M.; Daeyaert, F.; Ludovici, D. W.; Kukla, M. J.; De Corte, B.; Kavash, R. W.; Ho, C. Y.; Ye, H.; Lichtenstein, M. A.; Andries, K.; Pauwels, R.; De Bethune, M.-P.; Boyer, P. L.; Clark, P.; Hughes, S. H.; Janssen, P. A. J.; Arnold, E. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (Etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J. Med. Chem. 2004, 47, 2550-2560.
9. Hsiou, Y.; Ding, J.; Das, K.; Clark, A. D., Jr.; Boyer, P. L.; Lewi, P.; Janssen, P. A. J.; Kleim, J.-P.; Rosner, M.; Hughes, S. H.; Arnold, E. The Lys103Asn Mutation of HIV-1 RT: A Novel Mechanism of Drug Resistance. J. Mol. Biol. 2001, 309, 437-445.
10. Jacobo-Molina, A.; Ding, J.; Nanni, R. G.; Clark, A. D., Jr.; Lu, X.; Tantillo, C.; Williams, R. L.; Kamer, G.; Ferris, A. L.; et al. Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0.ANG. resolution shows bent DNA. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6320-6324.
11. Babine, R. E.; Bender, S. L. Molecular Recognition of Protein-Ligand Complexes: Applications to Drug Design. Chem. Rev. 1997, 97, 1359-1472.
12. Greer, J.; Erickson, J. W.; Baldwin, J. J.; Varney, M. D. Application of the three-dimensional structures of protein target molecules in structure-based drug design. J. Med. Chem. 1994, 37, 1035-1054.
13. Kuntz, I. D. Structure-based strategies for drug design and discovery. Science 1992, 257, 1078-1082.
14. Stevens, R. C.; Yokoyama, S.; Wilson, I. A. Global efforts in structural genomics. Science 2001, 294, 89-92.
15. Halperin, I.; Ma, B.; Wolfson, H.; Nussinov, R. Principles of docking: an overview of search algorithms and a guide to scoring functions. Proteins: Struct. Funct. Genet. 2002, 47, 409-443.
16. Waszkowycz, B. New methods for structure-based de novo drug design. Adv. Drug Discov. Technol. 1998, 143-164.
17. Verdonk, M. L.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Taylor, R. D. Improved protein-ligand docking using GOLD. Proteins: Struct. Funct. Genet. 2003, 52, 609-623.
18. Eldridge, M. D.; Murray, C. W.; Auton, T. R.; Paolini, G. V.; Mee, R. P. 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. 1997, 11, 425-445.
19. Kramer, B.; Rarey, M.; Lengauer, T. Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking. Proteins: Struct. Funct. Genet. 1999, 37, 228-241.
20. Claussen, H.; Buning, C.; Rarey, M.; Lengauer, T. FlexE: efficient molecular docking considering Prot. Struc. variations. J. Mol. Biol. 2001, 308, 377-395.
21. 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.
22. Goodsell, D. S.; Morris, G. M.; Olson, A. J. Automated docking of flexible ligands: applications of AutoDock. J. Mol. Recognit. 1996, 9, 1-5.
23. Bursulaya, B. D.; Totrov, M.; Abagyan, R.; Brooks, C. L., III Comparative study of several algorithms for flexible ligand docking. J. Comput.-Aided Mol. Des. 2004, 17, 755-763.
24. Titmuss, S. J.; Keller, P. A.; Griffith, R. Docking experiments in the flexible non-nucleoside inhibitor binding pocket of HIV-1 reverse transcriptase. Bioorg. Med. Chem. 1999, 7, 1163-1170.
25. Halgren, T. A.; Murphy, R. B.; Friesner, R. A.; Beard, H. S.; Frye, L. L.; Pollard, W. T.; Banks, J. L. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 2004, 47, 1750-1759.
26. Zhou, Z.; Madrid, M.; Madura, J. D. Docking of non-nucleoside inhibitors: Neotripterifordin and its derivatives to HTV-1 reverse transcriptase. Proteins: Struct. Funct. Genet. 2002, 49, 529-542.
27. Daeyaert, F.; de Jonge, M.; Heeres, J.; Koymans, L.; Lewi, P.; Vinkers Maarten, H.; Janssen, P. A. J. A pharmacophore docking algorithm and its application to the cross-docking of 18 HIV-NNRTI's in their binding pockets. Proteins: Struct. Funct. Genet. 2004, 54, 526-533.
28. Ranise, A.; Spallarossa, A.; Schenone, S.; Bruno, O.; Bondavalli, F.; Vargiu, L.; Marceddu, T.; Mura, M.; La Colla, P.; Pani, A. Design, Synthesis, SAR, and Molecular Modeling Studies of Acylthiocarbamates: A Novel Series of Potent Non-nucleoside HIV-I Reverse Transcriptase Inhibitors Structurally Related to Phenethylthiazolylthiourea Derivatives. J. Med. Chem. 2003, 46, 768-781.
29. Ragno, R.; Mai, A.; Sbardella, G.; Artico, M.; Massa, S.; Musiu, C.; Mura, M.; Marturana, F.; Cadeddu, A.; La Colla, P. Computer-aided design, synthesis, and anti-HIV-1 activity in vitro of 2-alkylamino-6-[l-(2,6- difluorophenyl)alkyl]-3,4-dihydro-5-alkyl-pyrimidi n-4(3H)-ones as novel potent non-nucleoside reverse transcriptase inhibitors, also active against the Y181C variant. J. Med. Chem. 2004, 47, 928-934.
30. Silvestri, R.; De Martino, G.; Artico, M.; La Regina, G.; Ragno, R.; Loddo, R.; La Colla, P.; Marongiu, M. E.; La Colla, M.; Pani, A. Anti-HIV-1 NNRT agents: acylamino pyrryl aryl sulfones (APASs) as truncated analogues of tricyclic PBTDs. Med. Chem. Res. 2002, 11, 195-218.
31. Di Santo, R.; Costi, R.; Artico, M.; Ragno, R.; Massa, S.; La Colla, M.; Loddo, R.; La Colla, P.; Pani, A. Arylthiopyridylmethylisopropylpyrrole carbinols, novel NNRTIs endowed with potent anti-HIV-1 activity. Med. Chem. Res. 2002, 11, 153-167.
32. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Jones, E. Y.; Kirby, I.; Keeling, J.; Ross, C. K.; Larder, B. A.; Stuart, D. I.; Stammers, D. K. 3′-Azido-3′-deoxythymidine drug resistance mutations in HIV-I reverse transcriptase can induce long range conformational changes. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 9518-9523.
33. Ren, J.; Esnouf, R.; Garman, E.; Somers, D.; Ross, C.; Kirby, I.; Keeling, J.; Darby, G.; Jones, Y.; Stuart, D.; et al. High-resolution structures of HIV-1 RT from four RT-inhibitor complexes. Nat. Struct. Biol. 1995, 2, 293-302.
34. Chan, J. H.; Hong, J. S.; Hunter, R. N. R.; Orr, G. F.; Cowan, J. R.; Sherman, D. B.; Sparks, S. M.; Reitter, B. E.; Andrews, C. W. R.; Hazen, R. J.; St Clair, M.; Boone, L. R.; Ferris, R. G.; Creech, K. L.; Roberts, G. B.; Short, S. A.; Weaver, K.; Ott, R. J.; Ren, J.; Hopkins, A.; Stuart, D. I.; Stammers, D. K. 2-Amino-6-arylsulfonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1. J. Med. Chem. 2001, 44, 1866-1882.
35. Ding, J.; Das, K.; Moereels, H.; Koymans, L.; Andries, K.; Janssen, P. A.; Hughes, S. H.; Arnold, E. Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors. Nat. Struct. Biol. 1995, 2, 407-415.
36. Das, K.; Ding, J.; Hsiou, Y.; Clark, A. D. J.; Moereels, H.; Koymans, L.; Andries, K.; Pauwels, R.; Janssen, P. A.; Boyer, P. L.; Clark, P.; Smith, R. H. J.; Kroeger Smith, M. B.; Michejda, C. J.; Hughes, S. H.; Arnold, E. Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HTV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. J. Mol. Biol. 1996, 264, 1085-1100.
37. Ren, J.; Esnouf, R.; Hopkins, A.; Ross, C.; Jones, Y.; Stammers, D.; Stuart, D. The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO: lessons for inhibitor design. Structure 1995, 3, 915-926.
38. Esnouf, R. M.; Ren, J.; Hopkins, A. L.; Ross, C. K.; Jones, E. Y.; Stammers, D. K.; Stuart, D. I. Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis-(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 3984-3989.
39. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Stuart, D. I.; Stammers, D. K. Crystallographic analysis of the binding modes of thiazoloisoindolinone non-nucleoside inhibitors to HIV-1 reverse transcriptase and comparison with modeling studies. J. Med. Chem. 1999, 42, 3845-3851.
40. Ding, J.; Das, K.; Tantillo, C.; Zhang, W.; Clark, A. D. J.; Jessen, S.; Lu, X.; Hsiou, Y.; Jacobo-Molina, A.; Andries, K.; et al. Structure of HIV-1 reverse transcriptase in a complex with the nonnucleoside inhibitor alpha-APA R 95845 at 2.8 A resolution. Structure 1995, 3, 365-379.
41. Pauwels, R.; Andries, K.; Debyser, Z.; Van Daele, P.; Schols, D.; Stoffels, P.; De Vreese, K.; Woestenborghs, R.; Vandamme, A. M.; Janssen, C. G.; et al. Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 1711-1715.
42. Ren, J.; Milton, J.; Weaver, K. L.; Short, S. A.; Stuart, D. I.; Stammers, D. K. Structural basis for the resilience of efavirenz (DMP-266) to drug resistance mutations in HIV-1 reverse transcriptase. Struct. Fold. Des. 2000, 8, 1089-1094.
43. Corbett, J. W.; Ko, S. S.; Rodgers, J. D.; Jeffrey, S.; Bacheler, L. T.; Habe, R. M.; Diamond, S.; Lai, C. M.; Rabel, S. R.; Saye, J. A.; Adams, S. P.; Trainor, G. L.; Anderson, P. S.; Erickson-Viitanen, S. K. Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 1999, 43, 2893-2897.
44. Lindberg, J.; Sigurdsson, S.; Lowgren, S.; Andersson, H. O.; Sahlberg, C.; Noreen, R.; Fridborg, K.; Zhang, H.; Unge, T. Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. Eur. J. Biochem. 2002, 269, 1670-1677.
45. 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.
46. Hopkins, A. L.; Ren, J.; Tanaka, H.; Baba, M.; Okamato, M.; Stuart, D. I.; Stammers, D. K. Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants. J. Med. Chem. 1999, 42, 4500-4505.
47. Hsiou, Y.; Das, K.; Ding, J.; Clark, A. D. J.; Kleim, J. P.; Rosner, M.; Winkler, I.; Riess, G.; Hughes, S. H.; Arnold, E. Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. J. Mol. Biol. 1998, 284, 313-323.
48. Hopkins, A. L.; Ren, J.; Esnouf, R. M.; Willcox, B. E.; Jones, E. Y.; Ross, C.; Miyasaka, T.; Walker, R. T.; Tanaka, H.; Stammers, D. K.; Stuart, D. I. Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors. J. Med. Chem. 1996, 39, 1589-1600.
49. Hogberg, M.; Sahlberg, C.; Engelhardt, P.; Noreen, R.; Kangasmetsa, J.; Johansson, N. G.; Oberg, B.; Vrang, L.; Zhang, H.; BL, S.; Unge, T.; Lovgren, S.; Fridborg, K.; Backbro, K. Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues. J. Med. Chem. 1999, 42, 4150-4160.
50. Ren, J.; Diprose, J.; Warren, J.; Esnouf, R. M.; Bird, L. E.; Ikemizu, S.; Slater, M.; Milton, J.; Balzarini, J.; Stuart, D. I.; Stammers, D. K. Phenylethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptases. Structural and biochemical analyses. J. Biol. Chem. 2000, 275, 5633-5639.
51. Ren, J.; Nichols, C.; Bird, L. E.; Fujiwara, T.; Sugimoto, H.; Stuart, D. I.; Stammers, D. K. Binding of the second generation non-nucleoside inhibitor S-1153 to HIV-1 reverse transcriptase involves extensive main chain hydrogen bonding. J. Biol. Chem. 2000, 275, 14316-14320.
52. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Warren, J.; Balzarini, J.; Stuart, D. I.; Stammers, D. K. Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives. Biochemistry 1998, 37, 14394-14403.
53. Wang, J.; Morin, P.; Wang, W.; Kollman, P. A. Use of MM-PBSA in reproducing the binding free energies to HIV-1 RT of TIBO derivatives and predicting the binding mode to HIV-1 RT of efavirenz by docking and MM-PBSA. J. Am. Chem. Soc. 2001, 123, 5221-5230.
54. Rao, G. S.; Bhatnagar, S. In silico structure-based design of a potent, mutation resilient, small peptide inhibitor of HIV-1 reverse transcriptase. J. Biomol. Struct. Dyn. 2003, 21, 171-178.
55. Ragno, R.; Mai, A.; Massa, S.; Cerbara, I.; Valente, S.; Bottoni, P.; Scatena, R.; Jesacher, F.; Loidl, P.; Brosch, G. 3-(4-Aroyl-1-methyl-1H-pyrrol- 2-yl)-N-hydroxy-2-propenamides as a New Class of Synthetic Histone Deacetylase Inhibitors. 3. Discovery of Novel Lead Compounds through Structure-Based Drug Design and Docking Studies. J. Med. Chem. 2004, 47, 1351-1359.
56. Hsiou, Y.; Ding, J.; Das, K.; Clark, A. D., Jr.; Hughes, S. H.; Arnold, E. Structure of unliganded HIV-1 reverse transcriptase at 2.7.ANG. resolution: implications of conformational changes for polymerization and inhibition mechanisms. Structure 1996, 4, 853-860.
57. Jager, J.; Smerdon, S. J.; Wang, J.; Boisvert, D. C.; Steitz, T. A. Comparison of three different crystal forms shows HIV-1 reverse transcriptase displays an internal swivel motion. Structure 1994, 2, 869-876.
58. Patel, P. H.; Jacobo-Molina, A.; Ding, J.; Tantillo, C.; Clark, A. D., Jr.; Raag, R.; Nanni, R. G.; Hughes, S. H.; Arnold, E. Insights into DNA polymerization mechanisms from structure and function analysis of HIV-1 reverse transcriptase. Biochemistry 1995, 34, 5351-5363.
59. Kroeger Smith, M. B.; Rouzer, C. A.; Taneyhill, L. A.; Smith, N. A.; Hughes, S. H.; Boyer, P. L.; Janssen, P. A.; Moereels, H.; Koymans, L.; Arnold, E.; et al. Molecular modeling studies of HIV-1 reverse transcriptase nonnucleoside inhibitors: total energy of complexation as a predictor of drug placement and activity. Protein Sci. 1995, 4, 2203-2222.
60. Birch, L.; Murray, C. W.; Hartshorn, M. J.; Tickle, I. J.; Verdonk, M. L. Sensitivity of molecular docking to induced fit effects in influenza virus neuraminidase. J. Comput.-Aided Mol. Des. 2003, 16, 855-869.
61. Carlson, H. A.; McCammon, J. A. Accommodating protein flexibility in computational drug design. Mol. Pharm. 2000, 57, 213-218.
62. Osterberg, F.; Morris, G. M.; Sanner, M. F.; Olson, A. J.; Goodsell, D. S. Automated docking to multiple target structures: incorporation of protein mobility and structural water heterogeneity in Autodock. Proteins: Struct. Funct. Genet. 2001, 46, 34-40.
63. Vieth, M.; Hirst, J. D.; Kolinski, A.; Brooks, C. L., III Assessing energy functions for flexible docking. J. Comput. Chem. 1998, 19, 1612-1622.
64. Ragno, R.; Artico, M.; De Martino, G.; La Regina, G.; Coluccia, A.; Di Pasquali, A.; Silvestri, R. Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones (IASs). Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl) carboxyamide and N-(2-Hydroxyethyl)carboxy hydrazide Derivatives. J. Med. Chem., in press.
65. Silvestri, R.; De Le Martino, G.; La Regina, G.; Artico, M.; Massa, S.; Vargiu, L.; Mura, M.; Loi, A. G.; Marceddu, T.; La Colla, P. Novel Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI Resistance Mutations: Synthesis and SAR Studies. J. Med. Chem. 2003, 46, 2482-2493.
66. Berman, H.; Henrick, K.; Nakamura, H. Announcing the worldwide Protein Data Bank. Nat. Struct. Biol. 2003, 10, 980.
67. Berman, H. M.; Westbrook, J.; Zardecki, C.; Bourne, P. E. The protein data bank. Prot. Struct. 2003, 389-405.
68. 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.
69. Martin, A. C. R. Profit 2.2; http://www.bioinf.org.uk/software/profit/.
70. McLachlan, A. D. Rapid comparison of Prot. Struc. Acta Crystallogr., Sect. A: Fundam. Crystallogr. 1982, A38, 871-873.
71. Huang, C. C.; Couch, G. S.; Pettersen, E. F.; Ferrin, T. E. In Chimera: An Extensible Molecular Modeling Application Constructed Using Standard Components; Pacific Symposium on Biocomputing: 1996, 1, 724.
72. Maestro 3.1; Schrodinger, Inc.: Portland, OR, 2001.
73. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel-An Integrated Software System for Modeling Organic and Bioorganic Molecules Using Molecular Mechanics. J. Comput. Chem. 1990, 11, 440-467.
74. Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham, T. E., III; DeBolt, S.; Ferguson, D.; Seibel, G.; Kollman, P. "AMBER", a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to stimulate the structural and energetic properties of molecules. Comput. Phys. Comm. 1995, 91, 1-42.
75. Sotriffer, C. A.; Ni, H. H.; McCammon, J. A. Binding modes of HIV-1 integrase inhibitors at the active site. Rational Approaches to Drug Design, Proceedings of the European Symposium on Quantitative Structure-Activity Relationships, 13th, Duesseldorf, Germany, Aug 27 to Sept 1, 2000; Prous Science: Barcelona, Spain, 2001; pp 83-87.