Elucidating the Inhibition Mechanism of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors through Multicopy Molecular Dynamics Simulations

Journal of Molecular Biology

Volumn 388, Issue 3, 2009, Pages 644-658

  Ivetac, Anthony ^a   McCammon, J Andrew ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

HIV; molecular dynamics; reverse transcriptase; simulation

Indexed keywords

NEVIRAPINE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ALLOSTERISM; ARTICLE; CATALYSIS; CONFORMATIONAL TRANSITION; CRYSTALLOGRAPHY; ENZYME ACTIVITY; GEOMETRY; HUMAN IMMUNODEFICIENCY VIRUS 1; METHODOLOGY; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SIMULATION; VIRUS INHIBITION;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 64649104893     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2009.03.037     Document Type: Article

References (75)

1. Mathers C.D., and Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 3 (2006) e442
2. De Clercq E. The design of drugs for HIV and HCV. Nat. Rev. Drug Discov. 6 (2007) 1001-1018
3. Pomerantz R.J., and Horn D.L. Twenty years of therapy for HIV-1 infection. Nat. Med. 9 (2003) 867-873
4. Sarafianos S.G., Marchand B., Das K., Himmel D., Parniak M.A., Hughes S.H., and Arnold E. Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition. J. Mol. Biol. 385 (2009) 693-713
5. De Clercq E. New developments in anti-HIV chemotherapy. Biochim. Biophys. Acta 1587 (2002) 258-275
6. De Clercq E. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): past, present, and future. Chem. Biodivers. 1 (2004) 44-64
7. Petit F., Fromenty B., Owen A., and Estaquier J. Mitochondria are sensors for HIV drugs. Trends Pharmacol. Sci. 26 (2005) 258-264
8. Ren J., and Stammers D.K. HIV reverse transcriptase structures: designing new inhibitors and understanding mechanisms of drug resistance. Trends Pharmacol. Sci. 26 (2005) 4-7
9. Sarafianos S.G., Das K., Hughes S.H., and Arnold E. Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases. Curr. Opin. Struct. Biol. 14 (2004) 716-730
10. Campiani G., Ramunno A., Maga G., Nacci V., Fattorusso C., Catalanotti B., et al. Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: past, present, and future perspectives. Curr. Pharm. Des. 8 (2002) 615-657
11. Pauwels R. New non-nucleoside reverse transcriptase inhibitors (NNRTIs) in development for the treatment of HIV infections. Curr. Opin. Pharmacol. 4 (2004) 437-446
12. Ripamonti D., and Maggiolo F. Rilpivirine, a non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection. Curr. Opin. Investig. Drugs 9 (2008) 899-912
13. Seminari E., Castagna A., and Lazzarin A. Etravirine for the treatment of HIV infection. Expert Rev. Anti-Infect. Ther. 6 (2008) 427-433
14. Das K., Clark Jr. A.D., Lewi P.J., Heeres J., De Jonge M.R., Koymans L.M., et al. 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 (2004) 2550-2560
15. Das K., Sarafianos S.G., Arnold E., Hughes S.H., William J.L., and Lane M.D. HIV-1 reverse transcriptase structure. Encyclopedia of Biological Chemistry (2004), Elsevier, New York 388-392
16. Lawtrakul L., Beyer A., Hannongbua S., and Wolschann P. Quantitative structural rearrangement of HIV-1 reverse transcriptase on binding to non-nucleoside inhibitors. Monatsh. Chem. 135 (2004) 1033-1046
17. Arnold E., Das K., Ding J., Yadav P.N., Hsiou Y., Boyer P.L., and Hughes S.H. Targeting HIV reverse transcriptase for anti-AIDS drug design: structural and biological considerations for chemotherapeutic strategies. Drug Des. Discov. 13 (1996) 29-47
18. Rodgers D.W., Gamblin S.J., Harris B.A., Ray S., Culp J.S., Hellmig B., et al. The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1. Proc. Natl Acad. Sci. USA 92 (1995) 1222-1226
19. Ding J., Das K., Hsiou Y., Sarafianos S.G., Clark Jr. A.D., Jacobo-Molina A., et al. Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 Å resolution. J. Mol. Biol. 284 (1998) 1095-1111
20. Huang H., Chopra R., Verdine G.L., and Harrison S.C. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282 (1998) 1669-1675
21. Hsiou Y., Das K., Ding J., Clark Jr. A.D., Kleim J.P., Rosner M., et al. 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 (1998) 313-323
22. Ren J., Nichols C., Bird L.E., Fujiwara T., Sugimoto H., Stuart D.I., and 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. 275 (2000) 14316-14320
23. Das K., Ding J., Hsiou Y., Clark Jr. A.D., Moereels H., Koymans L., et al. Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. J. Mol. Biol. 264 (1996) 1085-1100
24. Beyer A., Lawtrakul L., Hannongbua S., and Wolschann P. Systematic investigation of non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Monatsh. Chem. 135 (2004) 1047-1059
25. Ren J., and Stammers D.K. Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase. Virus Res. 134 (2008) 157-170
26. Esnouf R., Ren J., Ross C., Jones Y., Stammers D., and Stuart D. Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors. Nat. Struct. Biol. 2 (1995) 303-308
27. Kohlstaedt L.A., Wang J., Friedman J.M., Rice P.A., and Steitz T.A. Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256 (1992) 1783-1790
28. Spence R.A., Kati W.M., Anderson K.S., and Johnson K.A. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 267 (1995) 988-993
29. Rittinger K., Divita G., and Goody R.S. Human immunodeficiency virus reverse transcriptase substrate-induced conformational changes and the mechanism of inhibition by nonnucleoside inhibitors. Proc. Natl Acad. Sci. USA 92 (1995) 8046-8049
30. Liu S.X., Abbondanzieri E.A., Rausch J.W., Le Grice S.F.J., and Zhuang X.W. Slide into action: dynamic shuttling of HIV reverse transcriptase on nucleic acid substrates. Science 322 (2008) 1092-1097
31. Madrid M., Jacobo-Molina A., Ding J., and Arnold E. Major subdomain rearrangement in HIV-1 reverse transcriptase simulated by molecular dynamics. Proteins 35 (1999) 332-337
32. Madrid M., Lukin J.A., Madura J.D., Ding J., and Arnold E. Molecular dynamics of HIV-1 reverse transcriptase indicates increased flexibility upon DNA binding. Proteins 45 (2001) 176-182
33. Shen L., Shen J., Luo X., Cheng F., Xu Y., Chen K., et al. Steered molecular dynamics simulation on the binding of NNRTI to HIV-1 RT. Biophys. J. 84 (2003) 3547-3563
34. Zhou Z., Madrid M., Evanseck J.D., and Madura J.D. Effect of a bound non-nucleoside RT inhibitor on the dynamics of wild-type and mutant HIV-1 reverse transcriptase. J. Am. Chem. Soc. 127 (2005) 17253-17260
35. Bahar I., Erman B., Jernigan R.L., Atilgan A.R., and Covell D.G. Collective motions in HIV-1 reverse transcriptase: examination of flexibility and enzyme function. J. Mol. Biol. 285 (1999) 1023-1037
36. Sluis-Cremer N., Temiz N.A., and Bahar I. Conformational changes in HIV-1 reverse transcriptase induced by nonnucleoside reverse transcriptase inhibitor binding. Curr. HIV Res. 2 (2004) 323-332
37. Temiz N.A., and Bahar I. Inhibitor binding alters the directions of domain motions in HIV-1 reverse transcriptase. Proteins 49 (2002) 61-70
38. Caves L.S., Evanseck J.D., and Karplus M. Locally accessible conformations of proteins: multiple molecular dynamics simulations of crambin. Protein Sci. 7 (1998) 649-666
39. Gorfe A.A., Grant B.J., and McCammon J.A. Mapping the nucleotide and isoform-dependent structural and dynamical features of Ras proteins. Structure 16 (2008) 885-896
40. van Aalten D.M., Conn D.A., de Groot B.L., Berendsen H.J., Findlay J.B., and Amadei A. Protein dynamics derived from clusters of crystal structures. Biophys. J. 73 (1997) 2891-2896
41. Amadei A., Linssen A.B., and Berendsen H.J. Essential dynamics of proteins. Proteins 17 (1993) 412-425
42. Mao B., Pear M.R., McCammon J.A., and Quiocho F.A. Hinge-bending in l-arabinose-binding protein. The "Venus's-flytrap" model. J. Biol. Chem. 257 (1982) 1131-1133
43. Hermann T., and Heumann H. Strained template under the thumbs. How reverse transcriptase of human immunodeficiency virus type 1 moves along its template. Eur. J. Biochem. 242 (1996) 98-103
44. Cregut D., Drin G., Liautard J.P., and Chiche L. Hinge-bending motions in annexins: molecular dynamics and essential dynamics of apo-annexin V and of calcium bound annexin V and I. Protein Eng. 11 (1998) 891-900
45. van Aalten D.M., Findlay J.B., Amadei A., and Berendsen H.J. Essential dynamics of the cellular retinol-binding protein-evidence for ligand-induced conformational changes. Protein Eng. 8 (1995) 1129-1135
46. Peters G.H., van Aalten D.M., Svendsen A., and Bywater R. Essential dynamics of lipase binding sites: the effect of inhibitors of different chain length. Protein Eng. 10 (1997) 149-158
47. de Groot B.L., Hayward S., van Aalten D.M., Amadei A., and Berendsen H.J. Domain motions in bacteriophage T4 lysozyme: a comparison between molecular dynamics and crystallographic data. Proteins 31 (1998) 116-127
48. van Aalten D.M., Amadei A., Linssen A.B., Eijsink V.G., Vriend G., and Berendsen H.J. The essential dynamics of thermolysin: confirmation of the hinge-bending motion and comparison of simulations in vacuum and water. Proteins 22 (1995) 45-54
49. Wriggers W., and Schulten K. Protein domain movements: detection of rigid domains and visualization of hinges in comparisons of atomic coordinates. Proteins 29 (1997) 1-14
50. Mukhopadhyay J., Das K., Ismail S., Koppstein D., Jang M., Hudson B., et al. The RNA polymerase "switch region" is a target for inhibitors. Cell 135 (2008) 295-307
51. Xia Q., Radzio J., Anderson K.S., and Sluis-Cremer N. Probing nonnucleoside inhibitor-induced active-site distortion in HIV-1 reverse transcriptase by transient kinetic analyses. Protein Sci. 16 (2007) 1728-1737
52. Hamelberg D., Mongan J., and McCammon J.A. Accelerated molecular dynamics: a promising and efficient simulation method for biomolecules. J. Chem. Phys. 120 (2004) 11919-11929
53. Sugita Y., and Okamoto Y. Replica-exchange molecular dynamics method for protein folding. Chem. Phys. Lett. 314 (1999) 141-151
54. Grubmüller H. Predicting slow structural transitions in macromolecular systems: Conformational flooding. Phys. Rev. E 52 (1995) 2893
55. Amadei A., Linssen A.B., de Groot B.L., van Aalten D.M., and Berendsen H.J. An efficient method for sampling the essential subspace of proteins. J. Biomol. Struct. Dyn. 13 (1996) 615-625
56. Amaro R.E., Schnaufer A., Interthal H., Hol W., Stuart K.D., and McCammon J.A. Discovery of drug-like inhibitors of an essential RNA-editing ligase in Trypanosoma brucei. Proc. Natl Acad. Sci. USA 105 (2008) 17278-17283
57. Lin J.H., Perryman A.L., Schames J.R., and McCammon J.A. Computational drug design accommodating receptor flexibility: the relaxed complex scheme. J. Am. Chem. Soc. 124 (2002) 5632-5633
58. Lin J.H., Perryman A.L., Schames J.R., and McCammon J.A. The relaxed complex method: accommodating receptor flexibility for drug design with an improved scoring scheme. Biopolymers 68 (2003) 47-62
59. Ren J., Esnouf R., Garman E., Somers D., Ross C., Kirby I., et al. High resolution structures of HIV-1 RT from four RT-inhibitor complexes. Nat. Struct. Biol. 2 (1995) 293-302
60. van Aalten D.M., Bywater R., Findlay J.B., Hendlich M., Hooft R.W., and Vriend G. PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules. J. Comput.-Aided Mol. Des. 10 (1996) 255-262
61. Case D.A., Darden T.A., Cheatham III T.E., Simmerling C.L., Wang J., Duke R.E., et al. AMBER 10 (2008), University of California, San Francisco, CA
62. Frisch M.J.T., Schlegel G.W., Scuseria H.B., Robb G.E., Cheeseman M.A., Montgomery J.R., et al. Gaussian 03 (2003), Gaussian, Inc, Pittsburgh, PA
63. Berendsen H.J.C., Postma J.P.M., van Gunsteren W.F., Dinola A., and Haak J.R. Molecular-dynamics with coupling to an external bath. J. Chem. Phys. 81 (1984) 3684-3690
64. Hoover W.G. Canonical dynamics-equilibrium phase-space distributions. Phys. Rev. A 31 (1985) 1695-1697
65. Nose S. A molecular-dynamics method for simulations in the canonical ensemble. Mol. Phys. 52 (1984) 255-268
66. Parrinello M., and Rahman A. Polymorphic transitions in single-crystals-a new molecular-dynamics method. J. Appl. Phys. 52 (1981) 7182-7190
67. Darden T., York D., and Pedersen L. Particle mesh Ewald-an N·Log(N) method for Ewald sums in large systems. J. Chem. Phys. 98 (1993) 10089-10092
68. Hermans J., Berendsen H.J.C., van Gunsteren W.F., and Postma J.P.M. A consistent empirical potential for water-protein interactions. Biopolymers 23 (1984) 1513-1518
69. Hess B., Bekker H., Berendsen H.J.C., and Fraaije J. LINCS: a linear constraint solver for molecular simulations. J. Comput. Chem. 18 (1997) 1463-1472
70. Berendsen H.J.C., van der Spoel D., and Vandrunen R. Gromacs-a message-passing parallel molecular-dynamics implementation. Comput. Phys. Commun. 91 (1995) 43-56
71. Lindahl E., Hess B., and van der Spoel D. GROMACS 3.0: a package for molecular simulation and trajectory analysis. J. Mol. Model. 7 (2001) 306-317
72. van der Spoel D., Lindahl E., Hess B., Groenhof G., Mark A.E., and Berendsen H.J. GROMACS: fast, flexible, and free. J. Comput. Chem. 26 (2005) 1701-1718
73. Oostenbrink C., Villa A., Mark A.E., and van Gunsteren W.F. A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force-field parameter sets 53A5 and 53A6. J. Comput. Chem. 25 (2004) 1656-1676
74. Scott W.R.P., Hunenberger P.H., Tironi I.G., Mark A.E., Billeter S.R., Fennen J., et al. The GROMOS biomolecular simulation program package. J. Phys. Chem. A 103 (1999) 3596-3607
75. Humphrey, W., Dalke, A. & Schulten, K. (1996). VMD: visual molecular dynamics. J. Mol. Graphics, 14, 33-38, 27-28.