Artificial Intelligence in Medicine
Volume 45, Issue 2 , Pages 197-206 , February 2009

Computational proteomics analysis of binding mechanisms and molecular signatures of the HIV-1 protease drugs

  • Gennady Verkhivker

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1 785 864 1978; fax: +1 785 864 5558.

Received 28 November 2007 ,Revised 12 August 2008 ,Accepted 19 August 2008.

References 

  1. Wlodawer A, Erickson JW. Structure-based inhibitors of HIV-1 protease. Annu Rev Biochem. 1993;62:543–585
  2. Wlodawer A, Vondrasek J. Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. Annu Rev Biophys Biomol Struct. 1998;27:249–284
  3. Vondrasek J, Wlodawer A. HIVdb: a database of the structures of human immunodeficiency virus protease. Proteins. 2002;49(4):429–431
  4. Wlodawer A. Rational approach to AIDS drug design through structural biology. Annu Rev Med. 2002;53:595–614
  5. Ishima R, Freedberg DI, Wang YX, Louis JM, Torchia DA. Flap opening and dimer-interface flexibility in the free and inhibitor bound HIV protease and their implications for function. Structure. 1999;7(9):1047–1055
  6. Ishima R, Torchia DA. Protein dynamics from NMR. Nat Struct Biol. 2000;7(9):740–743
  7. Freedberg DI, Ishima R, Jacob J, Wang YX, Kustanovich I, Louis JM. Rapid structural fluctuations of the free HIV protease flaps in solution: relationship to crystal structures and comparison with predictions of dynamics calculations. Protein Sci. 2002;11(2):221–232
  8. Katoh E, Louis JM, Yamazaki T, Gronenborn AM, Torchia DA, Ishima R. A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Protein Sci 2003;12(7):1376–85.
  9. Hamelberg D, McCammon JA. Fast peptidyl cis–trans isomerization within the flexible Gly-rich flaps of HIV-1 protease, J Am Chem Soc 2005;127(40):13778–9.
  10. Scott WR, Schiffer CA. Curling of flap tips in HIV-1 protease as a mechanism for substrate entry and tolerance of drug resistance. Structure. 2000;8(12):1259–1265
  11. Perryman AL, Lin JH, McCammon JA. HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: possible contributions to drug resistance and a potential new target site for drugs. Protein Sci. 2004;13(4):1108–1123
  12. Perryman AL, Lin JH, McCammon JA. Restrained molecular dynamics simulations of HIV-1 protease: the first step in validating a new target for drug design. Biopolymers. 2006;82(3):272–284
  13. Perryman AL, Lin JH, McCammon JA. Optimization and computational evaluation of a series of potential active site inhibitors of the V82F/I84V drug-resistant mutant of HIV-1 protease: an application of the relaxed complex method of structure-based drug design. Chem Biol Drug Des. 2006;67(5):336–345
  14. Tozzini V, McCammon JA. A coarse grained model for the dynamics of flap opening in HIV-1 protease. Chem Phys Lett. 2005;413:123–128
  15. Tozzini V, Trylska J, Chang CE, McCammon JA. Flap opening dynamics in HIV-1 protease explored with a coarse-grained model. J Struct Biol. 2007;157(3):606–615
  16. Chang CE, Shen T, Trylska J, Tozzini V, McCammon JA. Gated binding of ligands to HIV-1 protease: Brownian dynamics simulations in a coarse-grained model. Biophys J. 2007;92(12):4179–4187
  17. Chang CE, Trylska J, Tozzini V, McCammon JA. Binding pathways of ligands to HIV-1 protease: coarse-grained and atomistic simulations. Chem Biol Drug Des. 2007;69(1):5–13
  18. Hornak V, Okur A, Rizzo RC, Simmerling C. HIV-1 protease flaps spontaneously open and reclose in molecular dynamics simulations. Proc Natl Acad Sci USA. 2006;103(4):915–920
  19. Hornak V, Okur A, Rizzo RC, Simmerling C. HIV-1 protease flaps spontaneously close to the correct structure in simulations following manual placement of an inhibitor into the open state. J Am Chem Soc. 2006;128(9):2812–2813
  20. Martin P, Vickrey JF, Proteasa G, Jimenez YL, Wawrzak Z, Winters MA. “Wide-open” 1.3 A structure of a multidrug-resistant HIV-1 protease as a drug target. Structure. 2005;13(12):1887–1895
  21. Layten M, Hornak V, Simmerling C. The open structure of a multi-drug-resistant HIV-1 protease is stabilized by crystal packing contacts. J Am Chem Soc. 2006;128(41):13360–13361
  22. Wallqvist A, Smythers GW, Covell DG. A cooperative folding unit in HIV-1 protease. Implications for protein stability and occurrence of drug-induced mutations. Protein Eng. 1998;11(11):999–1005
  23. Bhavesh NS, Sinha R, Mohan PM, Hosur RV. NMR elucidation of early folding hierarchy in HIV-1 protease. J Biol Chem. 2003;278(22):19980–19985
  24. Chatterjee A, Hosur RV. Following autolysis in proteases by NMR: insights into multiple unfolding pathways and mutational plasticities. Biophys Chem. 2006;123(1):1–10
  25. Ishima R, Ghirlando R, Tozser J, Gronenborn AM, Torchia DA, Louis JM. Folded monomer of HIV-1 protease. J Biol Chem. 2001;276(52):49110–49116
  26. Louis JM, Ishima R, Nesheiwat I, Pannell LK, Lynch SM, Torchia DA. Revisiting monomeric HIV-1 protease. Characterization and redesign for improved properties. J Biol Chem. 2003;278(8):6085–6092
  27. Ishima R, Torchia DA, Lynch SM, Gronenborn AM, Louis JM. Solution structure of the mature HIV-1 protease monomer: insight into the tertiary fold and stability of a precursor. J Biol Chem. 2003;278(44):43311–43319
  28. Ishima R, Torchia DA, Louis JM. Mutational and structural studies aimed at characterizing the monomer of HIV-1 protease and its precursor. J Biol Chem. 2007;282(23):17190–17199
  29. Louis JM, Dyda F, Nashed NT, Kimmel AR, Davies DR. Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease. Biochemistry. 1998;37(8):2105–2110
  30. Velazquez-Campoy A, Todd MJ, Freire E. HIV-1 protease inhibitors: enthalpic versus entropic optimization of the binding affinity. Biochemistry. 2000;39(9):2201–2207
  31. Bouras A, Boggetto N, Benatalah Z, de Rosny E, Sicsic S, Reboud-Ravaux M. Design, synthesis, and evaluation of conformationally constrained tongs, new inhibitors of HIV-1 protease dimerization. J Med Chem. 1999;42(6):957–962
  32. Bowman MJ, Chmielewski J. Novel strategies for targeting the dimerization interface of HIV protease with cross-linked interfacial peptides. Biopolymers. 2002;66(2):126–133
  33. Merabet N, Dumond J, Collinet B, Van Baelinghem L, Boggetto N, Ongeri S. New constrained “molecular tongs” designed to dissociate HIV-1 protease dimer. J Med Chem. 2004;47(25):6392–6400
  34. Hwang YS, Chmielewski J. Development of low molecular weight HIV-1 protease dimerization inhibitors. J Med Chem. 2005;48(6):2239–2242
  35. Bowman MJ, Byrne S, Chmielewski J. Switching between allosteric and dimerization inhibition of HIV-1 protease. Chem Biol. 2005;12(4):439–444
  36. Bannwarth L, Kessler A, Pethe S, Collinet B, Merabet N, Boggetto N. Molecular tongs containing amino acid mimetic fragments: new inhibitors of wild-type and mutated HIV-1 protease dimerization. J Med Chem. 2006;49(15):4657–4664
  37. Schramm HJ, Boetzel J, Buttner J, Fritsche E, Gohring W, Jaeger E. The inhibition of human immunodeficiency virus proteases by ‘interface peptides’. Antiviral Res. 1996;30(2/3):155–170
  38. Frutos S, Tarrago T, Giralt E. A fast and robust 19F NMR-based method for finding new HIV-1 protease inhibitors. Bioorg Med Chem Lett. 2006;16(10):2677–2681
  39. Frutos S, Rodriguez-Mias RA, Madurga S, Collinet B, Reboud-Ravaux M, Ludevid D. Disruption of the HIV-1 protease dimer with interface peptides: structural studies using NMR spectroscopy combined with [2-(13)C]-Trp selective labeling. Biopolymers. 2007;88(2):164–173
  40. Levy Y, Caflisch A, Onuchic JN, Wolynes PG. The folding and dimerization of HIV-1 protease: evidence for a stable monomer from simulations. J Mol Biol. 2004;340(1):67–79
  41. Broglia RA, Tiana G, Sutto L, Provasi D, Simona F. Design of HIV-1-PR inhibitors that do not create resistance: blocking the folding of single monomers. Protein Sci. 2005;14(10):2668–2681
  42. Broglia RA, Provasi D, Vasile F, Ottolina G, Longhi R, Tiana G. A folding inhibitor of the HIV-1 protease. Proteins. 2006;62(4):928–933
  43. Bonomi M, Gervasio FL, Tiana G, Provasi D, Broglia RA, Parrinello M. Insight into the folding inhibition of the HIV-1 Protease by a small peptide. Biophys J. 2007;93(8):2813–2821
  44. Verkhivker G, Tiana G, Camilloni C, Provasi D, Broglia RA. Atomistic simulations of the HIV-1 protease folding inhibition. Biophys J. 2008;95(2):550–562
  45. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res. 2000;28(1):235–242
  46. Berendsen HJC, van der Spoel D, van Drunen R. GROMACS: a message-passing parallel molecular dynamics implementation. Comput Phys Commun. 1995;91:43–56
  47. Lindahl E, Hess B, van der Spoel D. GROMACS 3. 0: a package for molecular simulation and trajectory analysis. J Mol Mod. 2001;7:306–317
  48. Verkhivker GM. Computational proteomics of biomolecular interactions in the sequence and structure space of the tyrosine kinome: deciphering the molecular basis of the kinase inhibitors selectivity. Proteins. 2007;66(4):912–929
  49. Verkhivker GM. In silico profiling of tyrosine kinases binding specificity and drug resistance using Monte Carlo simulations with the ensembles of protein kinase crystal structures. Biopolymers. 2007;85(4):333–348
  50. Mayo SL, Olafson BD. Goddard WA III. DREIDING: a generic force field for molecular simulation. J Phys Chem. 1990;94:8897–8909
  51. Weiner SJ, Kollman PA, Case DA, Singh UC, Chio C, Alagona G. A new force field for molecular mechanical simulation of nucleic acids and proteins. J Am Chem Soc. 1984;106:765–784
  52. Cornell WD, Cieplak P, Bayly CL, Gould IR, Merz KM, Ferguson DM. A second generation force field for simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc. 1995;117:5179–5197
  53. Stouten PFW , Fr”ommel C, Nakamura H, Sander C. An effective solvation term based on atomic occupancies for use in protein simulations. Mol Simul. 1993;10:97–120
  54. Beutler TC, Mark AE, van Schaik RC, Gerber PR, van Gunsteren W. Avoiding singularities and numerical instabilities in free energy calculations based on molecular simulations. Chem Phys Lett. 1994;222:529–539
  55. Marinari E, Parisi G. Simulated tempering: a new Monte Carlo scheme. Europhys Lett. 1992;19:451–458
  56. Sugita Y, Okamoto Y. Replica-exchange molecular dynamics method for protein folding. Chem Phys Lett. 1999;314:141–151
  57. Verkhivker GM, Rejto PA, Bouzida D, Arthurs S, Colson AB, Freer ST. Navigating ligand–protein binding free energy landscapes: universality and diversity of protein folding and molecular recognition mechanisms. Chem Phys Lett. 2001;336:495–503
  58. Still WC, Tempczyk A, Hawley RC, Hendrickson T. Semianalytical treatment of solvation for molecular mechanics and dynamics. J Am Chem Soc. 1990;112:6127–6129
  59. Mohamadi F, Richards NGJ , Guida WC, Liskamp R, Lipton M, Caufield C. MacroModel—an integrated software system for modeling organic and bioorganic molecules using molecular mechanics. J Comput Chem. 1990;11:440–467
  60. Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res. 2000;33(12):889–897

PII: S0933-3657(08)00125-5

doi: 10.1016/j.artmed.2008.08.011

Artificial Intelligence in Medicine
Volume 45, Issue 2 , Pages 197-206 , February 2009

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