Molecular modeling calculations of HIV-1 reverse transcriptase nonnucleoside inhibitors: Correlation of binding energy with biological activity for novel 2-aryl-substituted benzimidazole analogues

Journal of Medicinal Chemistry

Volumn 46, Issue 10, 2003, Pages 1940-1947

  Kroeger Smith, Marilyn B ^a,b   Hose, Brian M ^b   Hawkins, Arie ^b   Lipchock, James ^b   Farnsworth, David W ^a   Rizzo, Robert C ^c   Tirado Rives, Julian ^c   Arnold, Edward ^d   Zhang, Wanyi ^d   Hughes, Stephen H ^a   Jorgensen, William L ^c   Michejda, Christopher J ^a   Smith Jr , Richard H ^b  

^a NATIONAL CANCER INSTITUTE   (United States)

^b MCDANIEL COLLEGE   (United States)

^c YALE UNIVERSITY   (United States)

^d RUTGERS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2,6 DIFLUOROBENZYL) 2 (2,6 DIFLUOROPHENYL) 4 METHYLBENZIMIDAZOLE; 1 (2,6 DIFLUOROBENZYL) 2 (2,6 DIFLUOROPHENYL)BENZIMIDAZOLE DERIVATIVE; 4,5,6,7 TETRAHYDROIMIDAZO[4,5,1 JK][1,4]BENZODIAZEPIN 2(1H) ONE; 4,5,6,7 TETRAHYDROIMIDAZO[4,5,1 JK][1,4]BENZODIAZEPINE 2(1H) THIONE; BENZIMIDAZOLE DERIVATIVE; LYSINE; NITROGEN; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CALCULATION; CORRELATION ANALYSIS; CRYSTALLOGRAPHY; DRUG ACTIVITY; ENERGY; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDROGEN BOND; MOLECULAR MODEL; MONTE CARLO METHOD; STATISTICAL ANALYSIS; STRUCTURE ANALYSIS;

BENZIMIDAZOLES; BENZODIAZEPINES; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; HIV-1 REVERSE TRANSCRIPTASE; MODELS, MOLECULAR; MONTE CARLO METHOD; PROTEIN BINDING; REVERSE TRANSCRIPTASE INHIBITORS; THERMODYNAMICS;

EID: 0038416105     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020271f     Document Type: Article

References (29)

1. Kopp, E. B.; Miglietla, J. J.; Shrutkowski, A. G.; Shih, C. K.; Grob, P. M.; Skoog, M. T. Steady state kinetics and inhibition of HIV-1 reverse transcriptase by a non-nucleoside dipyridodiazepinone, BI-RG-587, using a heteropolymeric template. Nucleic Acids Res. 1991, 19, 3035-3039.
2. Romero, D. L.; Bussa, M.; Tan, C. K.; Reusser, F.; Palmer, J. R.; Poppe, S. M.; Aristoff, P. A.; Downery, K. M.; So, A. G.; Resnick, L.; Tarpley, W. G. Nonnucleoside Reverse Transeriptase Inhibitors That Potently and Specifically Block Human Immunodeficiency Virus Type 1 Replication. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 8806-8810.
3. Kroeger Smith, M. B.; Michejda, C. J.; Hughes, S. H.; Boyer, P. L.; Janssen, P. A. J.; Andries, K.; Buckheit, R. W., Jr.; Smith, R. H., Jr. Molecular modeling of HIV-1 reverse transcriptase drug-resistant mutant strains: implications for the mechanism of polymerase action. Protein Eng. 1997, 10, 1379-1383.
4. Essex, J. W.; Severance, D. L.; Tirado-Rives, J.; Jorgensen, W. L. Monte Carlo Simulations for Proteins: Binding Affinities for Trypsin-Benzamidine Complexes via Free-Energy Pertubations. J. Phys. Chem. B 1997, 36, 9663-9669.
5. Lamb, M. L.; Tirado-Rives, J.; Jorgensen, W. L. Estimation of binding affinity for FKBP12 inhibitors by a linear response method. Bioorg. Med. Chem. 1999, 7, 851-860.
6. Åqvist, J.; Medina, C.; Samuelsson, J.-E. A new method for predicting binding affinity in comput-aided drug design. Protein Eng. 1994, 7, 385-391.
7. Carlson, H. A.; Jorgensen, W. L. An extended linear response method for determining free energies of hydration. J. Phys. Chem. 1995, 99, 10667-10673.
8. Mcdonald, N. A.; Carlson, H. A.; Jorgensen, W. L. Free energies of solvation in chloroform and water from a linear response approach. J. Phys. Org. Chem. 1997, 10, 563-576.
9. Jorgensen, W. L. MCPRO, version 1.6.5; Yale University: New Haven, CT, 1998.
10. Hertoz-Jones, D. K.; Jorgensen, W. L. Binding affinities for sulfonamide inhibitors with human thrombin using Monte Carlo simulations with a linear response method. J. Med. Chem. 1997, 40, 1539-1549.
11. Lamb, M. L.; Jorgensen, W. L. Investigations of neurotropic inhibitors of FK506 binding protein via Monte Carlo simulations. J. Med. Chem. 1998, 41, 3928-3939.
12. Smith, R. H., Jr.; Jorgensen, W. L.; Tirado-Rives, J.; Lamb, M. L.; Janssen, P. A. J.; Michejda, C. J.; Kroeger Smith, M. B. Prediction of binding affinities for TIBO inhibitors of HIV-1 reverse transcriptase using Monte Carlo simulations in a linear response method. J. Med. Chem. 1998, 41 (26), 5272-5286.
13. Kroeger Smith, M. B.; Lamb, M. L., Tirado-Rives, J.; Jorgensen, W. L.; Michejda, C. J.; Ruby, S. K.; Smith, R. H., Jr. Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the nonnucleoside inhibitor 8-Cl TIBO: Contribution of the L100I and Y181C variants to protein stability and biological activity. Protein Eng. 2000, 13, 413-421.
14. Rizzo, R. C.; Tirado-Rives, J.; Jorgensen, W. L. Estimation of binding affinities for HEPT and nevirapine analogs with HIV-1 reverse transcriptase via Monte Carlo simulations. J. Med Chem. 2001, 44, 145-154.
15. Rizzo, R. C.; Blagovic, M. U.; Wang, D.-P.; Watkins, E. K.; Smith, M. B.; K.; Smith, R. H., Jr.; Tirado-Rives, J.; Jorgensen, W. L. Prediction of Activity for Non-Nucleoside Inhibitors with HIV Reverse Transcriptase Based on Monte Carlo Simulations. J. Med. Chem. 2002, 45, 2970-2987.
16. Roth, T.; Morningstar, M. L.; Boyer, P. L.; Hughes, S. H.; Buckheit, R. W., Jr.; Michejda, C. J. Synthesis and biological activity of novel nonnucleoside inhibitors of HIV-1 reverse transcriptase. 2-Aryl-substituted benzimidazoles. J. Med. Chem. 1997, 40, 4199-4207.
17. Morningstar, M. L.; Roth, T.; Kroeger Smith, M. B.; Zajac, M.; Watson, K.; Bujacz, G.; Buckheit, R. W., Jr.; Michejda, C. J. Synthesis and biological activity of potent non-nucleoside inhibitors of HIV-1 reverse transcriptase that retain activity against mutant forms of the enzyme. Manuscript in preparation.
18. Arnold, E.; Zhang, W. To be published.
19. Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 1996, 118, 11225-11236.
20. Spartan, version 5.0.3; Wavefunction, Inc.: Irvine, CA, 1997.
21. Tirado-Rives, J. PEPZ, version 1.0; Yale University: New Haven, CT, 1999.
22. Jorgensen, W. L. BOSS, version 4.2; Yale University: New Haven, CT, 1998.
23. Ding, J.; Das, K.; Moereels, H.; Koymans, L.; Andries, K.; Janssen, P. A. J.; Hughes, S. H.; Arnold, E. Structure of HIV-1 RT/TIBO R86183 complex reveals remarkable similarity in the binding of diverse nonnucleoside inhibitors. Nat. Struct. Biol. 1995, 2, 407-415.
24. Buckheit, R. W., Jr. Personal communication.
25. 50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
26. JMP, version 3; SAS Institute, Inc.: Cary, NC, 1995.
27. Julias, J. G.; Ferris, A. L.; Boyer, P. L.; Hughes, S. H. Replication of Phenotypically Mixed Human Immunodeficiency Virus Type 1 Virions Containing Catalytically Active and Catalytically Inactive Reverse Transcriptase. J. Virol. 2001, 75, 6537-6546.
28. Duffy, E. M.; Jorgensen, W. L. Prediction of properties from simulations: Free energies of solvation in hexadecane, octanol, and water. J. Am. Chem. Soc. 2000, 122, 2878-2888.
29. Rizzo, R. C.; Jorgensen, W. L. OPLS All-Atom Model for Amines: Resolution of the Amine Hydration Problem. J. Am. Chem. Soc. 1999, 121, 4827-4836.