Drug Resistant Mechanism of Diaryltriazine Analog Inhibitors of HIV-1 Reverse Transcriptase Using Molecular Dynamics Simulation and 3D-QSAR

Chemical Biology and Drug Design

Volumn 77, Issue 1, 2011, Pages 63-74

  Li, Zeng ^a   Zhang, Hao ^a   Li, Yixue ^b   Zhang, Jian ^c   Chen, Hai Feng ^a,b  

^a SHANGHAI JIAO TONG UNIVERSITY   (China)

^b SHANGHAI CENTER FOR BIOINFORMATION TECHNOLOGY   (China)

^c SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

Diaryltriazine analog; Drug resistance; HIV 1 reverse transcriptase inhibitor; Molecular dynamics simulation; Three dimensional quantitative structure activity relationship

Indexed keywords

DIARYLTRIAZINE ANALOG; LYSINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RNA DIRECTED DNA POLYMERASE; TYROSINE; UNCLASSIFIED DRUG;

ARTICLE; COMPARATIVE MOLECULAR FIELD ANALYSIS; COMPARATIVE MOLECULAR SIMILARITY INDICES ANALYSIS; DRUG ACTIVITY; DRUG MECHANISM; DRUG STRUCTURE; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MOLECULAR DYNAMICS; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

AMINO ACID SUBSTITUTION; BINDING SITES; CELL LINE, TUMOR; DATABASES, FACTUAL; DRUG RESISTANCE, VIRAL; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; MOLECULAR DYNAMICS SIMULATION; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; REVERSE TRANSCRIPTASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZINES;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 78650161047     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2010.01049.x     Document Type: Article

References (49)

1. Ode H., Matsuyama S., Hata M., Hoshino T., Kakizawa J., Sugiura W. (2007) Mechanism of drug resistance due to N88S in CRF01_AE HIV-1 protease, analyzed by molecular dynamics simulations. J Med Chem;50:1768-1777.
2. Gottlieb M.S. (2001) AIDS--past and future. N Engl J Med;344:1788-1791.
3. Hopkins A.L., Ren J.S., Esnouf R.M., Willcox B.E., Jones E.Y., Ross C., Miyasaka T., Walker R.T., Tanaka H., Stammers D.K., Stuart D.I. (1996) 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;39:1589-1600.
4. Jonckheere H., Anne J., De Clercq E. (2000) The HIV-1 reverse transcription (RT) process as target for RT inhibitors. Med Res Rev;20:129-154.
5. Balzarini J., Pelemans H., Esnouf R., De Clercq E. (1998) A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781. AIDS Res Hum Retroviruses;14:255-260.
6. Das K., Bauman J.D., Clark A.D. Jr, Frenkel Y.V., Lewi P.J., Shatkin A.J., Hughes S.H., Arnold E. (2008) High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations. Proc Natl Acad Sci USA;105:1466-1471.
7. Xiong Y.Z., Chen F.E., Balzarini J., De Clercq E., Pannecouque C. (2008) Non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 11: structural modulations of diaryltriazines with potent anti-HIV activity. Eur J Med Chem;43:1230-1236.
8. Das K., Clark A.D., Lewi P.J., Heeres J., De Jonge M.R., Koymans L.M.H., Vinkers H.M. et al. (2004) 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;47:2550-2560.
9. Ludovici D.W., Kavash R.W., Kukla M.J., Ho C.Y., Ye H., De Corte B.L., Andries K. et al. (2001) Evolution of anti-HIV drug candidates part 2: Diaryltriazine (DATA) analogues. Bioorg Med Chem Lett;11:2229-2234.
10. Lewi P., Arnold E., Andries K., Bohets H., Borghys H., Clark A., Daeyaert F. et al. (2004) Correlations between factors determining the pharmacokinetics and antiviral activity of HIV-1 non-nucleoside reverse transcriptase inhibitors of the diaryltriazine and diarylpyrimidine classes of compounds. Drugs R D;5:245-257.
11. Xiong Y.Z., Chen F.E., Balzarini J., De Clercq E., Pannecouque C. (2009) Non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 13: synthesis of fluorine-containing diaryltriazine derivatives for in vitro anti-HIV evaluation against wild-type strain. Chem Biodivers;6:561-568.
12. Udier-Blagovic M., Watkins E.K., Tirado-Rives J., Jorgensen W.L. (2003) Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase. Bioorg Med Chem Lett;13:3337-3340.
13. Ren J., Nichols C.E., Chamberlain P.P., Weaver K.L., Short S.A., Stammers D.K. (2004) Crystal structures of HIV-1 reverse transcriptases mutated at Codons 100, 106 and 108 and mechanisms of resistance to non-nucleoside inhibitors. J Mol Biol;336:569-578.
14. Lindberg J., Sigurdsson S., Lowgren S., Andersson H.O., Sahlberg C., Noreen R., Fridborg K., Zhang H., Unge T. (2002) Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. Eur J Biochem;269:1670-1677.
15. Ren J., Nichols C., Bird L., Chamberlain P., Weaver K., Short S., Stuart D.I., Stammers D.K. (2001) 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;312:795-805.
16. Hsiou Y., Das K.Y., Ding J.P., Clark A.D., Kleim J.P., Rosner M., Winkler I., Riess G., Hughes S.H., Arnold E. (1998) 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;284:313-323.
17. Morris G.M., Goodsell D.S., Halliday R.S., Huey R., Hart W.E., Belew R.K., Olson A.J. (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem;19:1639-1662.
18. Morris G.M., Goodsell D.S., Huey R., Olson A.J. (1996) Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4. J Comput Aided Mol Des;10:293-304.
19. Case D.A., Pearlman D.A., Caldwell J.W., Cheatham T.E. III, Wang J., Ross W.S., Simmerling C.L. et al. (2004) AMBER 8 Manual. San Francisco: University of California.
20. Cieplak P., Caldwell J., Kollman P.A. (2001) Molecular mechanical models for organic and biological systems going beyond the atom centered two body additive approximations: aqueous solution free energies of methanol and N-methyl acetamide, nucleic acid base, and amide hydrogen bonding and chloroform/water partition coefficients of the nucleic acid bases. J Comput Chem;22:1048-1057.
21. Jorgensen W.L., Chandrasekhar J., Madura J.D., Impey R.W., Klein M.L. (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys;79:926-935.
22. Wang J., Wolf R.M., Caldwell J.W., Kollman P.A., Case D.A. (2004) Development and testing of general amber force field. J Comput Chem;25:1157-1174.
23. Rychaert J.P., Ciccotti G., Berendsen H.J.C. (1977) Numerical integration of Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. Comput Phys;23:327-341.
24. Darden T., York D., Pedersen L. (1993) Particle mesh Ewald: an N.log(N) method for Ewald sums in large systems. J Chem Phys;98:10089-10092.
25. Cramer R.D. III, Patterson D.E., Bunce J.D. (1988) Comparative molecular field analysis (CoMFA) 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc;110:5959-5967.
26. Clark M., Cramer R.D. (1993) The probability of chance correlation using partial least squares (PLS). Quant Struct Act Relat;12:137-145.
27. Klebe G., Abraham U., Mietzner T. (1994) Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J Med Chem;37:4130-4146.
28. Bohm M., St rzebecher J., Klebe G. (1999) Three-dimensional quantitative structure-activity relationship analyses using comparative molecular field analysis and comparative molecular similarity indices analysis to elucidate selectivity differences of inhibitors binding to trypsin, thrombin, and factor Xa. J Med Chem;42:458-477.
29. Chen H.F. (2008) Mechanism of coupled folding and binding in the siRNA-PAZ complex. J Chem Theory Comput;4:1360-1368.
30. Chen H.F. (2009) Aggregation mechanism investigation of the GIFQINS cross-beta amyloid fibril. Comput Biol Chem;33:41-45.
31. Chen H.F. (2009) Molecular dynamics simulation of phosphorylated KID post-translational modification. PLoS ONE;4:e6516.
32. Chen H.F., Fan B.T., Zhao C.Y., Xie L., Zhao C.H., Zhou T., Lee K.H., Allaway G. (2005) Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3', 4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs. J Comput Aided Mol Des;19:243-258.
33. Chen H.F., Luo R. (2007) Binding induced folding in p53-MDM2 complex. J Am Chem Soc;129:2930-2937.
34. Chen Y., He Y.J., Wu M., Yan G., Li Y., Zhang J., Chen H.F. (2010) Insight into the stability of cross-beta amyloid fibril from molecular dynamics simulation. Biopolymers;93:578-586.
35. Qin F., Chen Y., Li Y., Chen H.F. (2009) Induced fit of mRNA-TIS11D complex. J Chem Phys;131:115103.
36. Qin F., Chen Y., Wu M., Li Y., Zhang J., Chen H.F. (2010) Induced fit or conformational selection for RNA/U1A folding. RNA;16:1053-1061.
37. Wallace A.C., Laskowski R.A., Thornton J.M. (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng;8:127-134.
38. Barreca M.L., Rao A., De Luca L., Iraci N., Monforte A.M., Maga G., De Clercq E., Pannecouque C., Balzarini J., Chimirri A. (2007) Discovery of novel benzimidazolones as potent non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains. Bioorg Med Chem Lett;17:1956-1960.
39. Chen H.F., Yao X.J., Li Q., Yuan S.G., Panaye A., Doucet J.P., Fan B.T. (2003) Comparative study of non nucleoside inhibitors with HIV-1 reverse transcriptase based on 3D-QSAR and docking. SAR QSAR Environ Res;14:455-474.
40. Figueiredo A., Zelina S., Sluis-Cremer N., Tachedjian G. (2008) Impact of residues in the nonnucleoside reverse transcriptase inhibitor binding pocket on HIV-1 reverse transcriptase heterodimer stability. Curr HIV Res;6:130-137.
41. Li Z., Han J., Chen H.F. (2008) Revealing interaction mode between HIV-1 reverse transcriptase and diaryltriazine analog inhibitor. Chem Biol Drug Des;72:350-359.
42. Ragno R., Mai A., Sbardella G., Artico M., Massa S., Musiu C., Mura M., Marturana F., Cadeddu A., La Colla P. (2004) Computer-aided design, synthesis, and anti-HIV-1 activity in vitro of 2-alkylamino-6-[1-(2, 6-difluorophenyl)alkyl]-3, 4-dihydro-5-alkylpyrimidin- 4(3H)-ones as novel potent non-nucleoside reverse transcriptase inhibitors, also active against the Y181C variant. J Med Chem;47:928-934.
43. Weinzinger P., Hannongbua S., Wolschann P. (2005) Molecular mechanics PBSA ligand binding energy and interaction of Efavirenz derivatives with HIV-1 reverse transcriptase. J Enzyme Inhib Med Chem;20:129-134.
44. Pata J.D., Stirtan W.G., Goldstein S.W., Steitz T.A. (2004) Structure of HIV-1 reverse transcriptase bound to an inhibitor active against mutant reverse transcriptases resistant to other nonnucleoside inhibitors. Proc Natl Acad Sci USA;101:10548-10553.
45. Rodriguez-Barrios F., Balzarini J., Gago F. (2005) The molecular basis of resilience to the effect of the Lys103Asn mutation in non-nucleoside HIV-1 reverse transcriptase inhibitors studied by targeted molecular dynamics simulations. J Am Chem Soc;127:7570-7578.
46. Rodriguez-Barrios F., Gago F. (2004) Understanding the basis of resistance in the irksome Lys103Asn HIV-1 reverse transcriptase mutant through targeted molecular dynamics simulations. J Am Chem Soc;126:15386-15387.
47. Pelemans H., Esnouf R.M., Jonckheere H., De Clercq E., Balzarini J. (1998) Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase. J Biol Chem;273:34234-34239.
48. Shen L.L., Shen J.H., Luo X.M., Cheng F., Xu Y.C., Chen K.X., Arnold E., Ding J.P., Jiang H.L. (2003) Steered molecular dynamics simulation on the binding of NNRTI to HIV-1 RT. Biophys J;84:3547-3563.
49. Ren J.S., Stammers D.K. (2008) Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase. Virus Res;134:157-170.