Validation of a model for the complex of HIV-1 reverse transcriptase with nonnucleoside inhibitor TMC125

Journal of the American Chemical Society

Volumn 125, Issue 20, 2003, Pages 6016-6017

  Udier Blagović, Marina ^a   Tirado Rives, Julian ^a   Jorgensen, William L ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 CHLORO 4 (2 CYCLOPROPYLVINYL) 3,4 DIHYDRO 4 TRIFLUOROMETHYL 2(1H) QUINAZOLINONE; EFAVIRENZ; ETRAVIRINE; NEVIRAPINE; PYRIMIDINE DERIVATIVE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CRYSTAL STRUCTURE; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME STRUCTURE; MODEL; STRUCTURE ANALYSIS; VALIDATION PROCESS; X RAY ANALYSIS;

ANTI-HIV AGENTS; HIV-1 REVERSE TRANSCRIPTASE; MODELS, MOLECULAR; MUTAGENESIS; PYRIDAZINES; REPRODUCIBILITY OF RESULTS; REVERSE TRANSCRIPTASE INHIBITORS; THERMODYNAMICS;

EID: 0037613579     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja034308c     Document Type: Article

References (21)

1. De Clercq, E. Biochim. Biophys. Acta 2002, 1587, 258-275.
2. Decks. S. G. J. Acquired Immune Defic. Syndr. 2001, 26, S25-S33.
3. Gruzdev, B.; Rakhmanova, A.; De Dier, K.; Comhaire. S.; Baede-van Dijk, P.; van't Klooster, G. Abstracts of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Illinois, December 16-19, 2001, no. 668.
4. Ludovici, D. W.; De Corte, B. L.; Kukla, M. J.; Ye, H.; Ho, C. Y.; Lichtenstein, M. A.; Kavash, R. W.; Andries, K.; de Béthune, M.-P.; Azijn, H.; Pauwels, R.; Lewi, P. J.; Heeres, J.; Koymans, L. M. H.; de Jonge, M. R.; Van Aken, K. J. A.; Daeyaert, F. F. D.; Das, K.; Arnold, E.; Janssen, P. A. J. Bioorg. Med. Chem. Lett. 2001, 11, 2235-2239.
5. (a) Sorbera, L. A.; del Fresno, M.; Leeson, P. A.; Silvestre, J.; Rabasseda, X. Drugs Future 2002, 27(4), 331-338.
6. (b) Cohen, J. Special News Report: HIV/AIDS. Science 2002, 296, 2320-2324.
7. Kroeger Smith, M. B.; Lamb, M. L.; Tirado-Rives, J.; Jorgensen, W. L.; Michejda, C. J.; Ruby, S. K.; Smith, R. H., Jr. Protein Eng. 2000, 13, 413-421.
8. Rizzo, R. C.; Wang, D.; Tirado-Rives, J.; Jorgensen, W. L. J. J. Am. Chem. Soc. 2000, 122, 12898-12900.
9. Wang, D.; Rizzo, R. C.; Tirado-Rives. J.; Jorgensen, W. L. Bioorg. Med. Chem. Lett. 2001, 11, 2799-2802.
10. Ren, J.; Nichols, C.; Bird, L. E.; Fujiwara, T.; Sugimoto, H.; Stuart, D. I.; Stammers, D. K. J. Biol. Chem. 2000, 275, 14316-14320.
11. Jorgensen, W. L. GenMol, v. 1.8; Yale University: New Haven, CT, 2002. Multiple positions for the core pyrimidine were sampled along with all combinations of substituent conformers. The protein is rigid, although use of reduced atomic radii emulates some host flexibility.
12. Rizzo, R. C.; Udier-Blagović, M.; Wang, D.-P.; Watkins, E. K.; Kroeger Smith, M. B.; Smith, R. H., Jr.; Tirado-Rives, J.; Jorgensen, W. L. J. Med. Chem. 2002, 45, 2970-2987.
13. (a) Ren, J.; Milton, J.; Weaver, K. L.; Short, S. A.; Stuart, D. I.; Stammers, D. K. Structure 2000, 8, 1089-1094.
14. (b) Lindberg, J.; Sigurösson, S.; Löwgren, S.; Andersson, H. O.; Sahlberg, C.; Noréen, R.; Fridborg, K.; Zhang, H.; Unge, T. Eur. J. Biochem. 2002, 269, 1670-1688.
15. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Ross, C.; Jones, Y.; Stammers, D. K.; Stuart. D. I. Structure 1995, 3, 915-926.
16. 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. J. Med. Chem. 1996, 39, 1589-1600.
17. Ren. J.; Esnouf, R. M.; Hopkins, A. L.; Warren, J.; Balzarini, J.; Stuart, D. I.; Stammers, D. K. Biochemistry 1998, 37, 14394-14403.
18. Zwanzig, R. W. J. Chem. Phys. 1954, 22, 1420-1426.
19. For a discussion of FEP methodology, see: Jorgensen W. L. Free Energy Changes in Solution. In Encyclopedia of Computational Chemistry; Schleyer, P. v. R., Ed.; Wiley: New York, 1998; Vol. 2, pp 1061-1070.
20. The L100I mutation was completed in two steps, L → norvaline → I. Both FEPs were performed in 10 windows utilizing double-wide sampling. Each window consisted of 10 million configurations of solvent-only equilibration, 10 M configurations of full equilibration, and 20 M configurations of averaging. For additional protocols, see ref 7.
21. Jorgensen, W. L. MCPRO version 1.68; Yale University: New Haven, CT, 2001.