Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV-1 protease

Proteins: Structure, Function and Genetics

Volumn 70, Issue 3, 2008, Pages 678-694

  Altman, Michael D ^a   Nalivaika, Ellen A ^b   Prabu Jeyabalan, Moses ^b   Schiffer, Celia A ^b   Tidor, Bruce ^c,d  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^c Department of Electrical Engineering and Computer Science   (United States)

^d Massachusetts Institute of Technology   (United States)

Author keywords

Charge optimization; Dead end elimination; Protein design

Indexed keywords

PROTEINASE; RIBONUCLEASE H; RNA DIRECTED DNA POLYMERASE; THREONINE; VALINE;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ARTICLE; BINDING AFFINITY; COMPLEX FORMATION; CRYSTAL STRUCTURE; ENTROPY; ENZYME INACTIVATION; ENZYME SUBSTRATE; ENZYME SUBSTRATE COMPLEX; EXPERIMENTAL STUDY; GENE MUTATION; HUMAN IMMUNODEFICIENCY VIRUS 1; INHIBITION KINETICS; ISOTHERMAL TITRATION CALORIMETRY; MEASUREMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN STRUCTURE; THERMODYNAMICS; VIRUS MUTANT; VIRUS RESISTANCE;

AMINO ACID SUBSTITUTION; BINDING SITES; COMPUTATIONAL BIOLOGY; CRYSTALLOGRAPHY, X-RAY; HIV PROTEASE; HIV PROTEASE INHIBITORS; MUTATION; PEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS; THREONINE; VALINE;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 38549143261     PISSN: 08873585     EISSN: 10970134     Source Type: Journal    
DOI: 10.1002/prot.21514     Document Type: Article

References (85)

1. Larder BA, Kemp SD. Multiple mutations in HIV-1 reverse-transcriptase confer high-level resistance to zidovudine (AZT). Science 1989;246:1155-1158.
2. Coffin JM. HIV population-dynamics in-vivo: implications for genetic-variation, pathogenesis, and therapy. Science 1995;267:483-489.
3. Condra JH, Schleif WA, Blahy OM, Gabryelski LJ, Graham DJ, Quintero JC, Rhodes A, Robbins HL, Roth E, Shivaprakash M, Titus D, Yang T, Teppler H, Squires KE, Deutsch PJ, Emini EA. In-vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 1995;374:569-571.
4. Debouck C. The HIV-1 protease as a therapeutic target for AIDS. AIDS Res Hum Retroviruses 1992;8:153-164.
5. Molla A, Korneyeva M, Gao Q, Vasavanonda S, Schipper PJ, Mo HM, Markowitz M, Chernyavskiy T, Niu P, Lyons N, Hsu A, Granneman GR, Ho DD, Boucher CAB, Leonard JM, Norbeck DW, Kempf DJ. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med 1996;2:760-766.
6. Flexner C. HIV protease inhibitors. New Eng J Med 1998;338:1281-1292.
7. Croteau G, Doyon L, Thibeault D, McKercher G, Pilote L, Lamarre D. Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors. J Virol 1997;71:1089-1096.
8. Martinez-Picado J, Savara LV, Sutton L, D'Aquila RT. Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. J Virol 1999;73:3744-3752.
9. Weber IT, Wu J, Adomat J, Harrison RW, Kimmel AR, Wondrak EM, Louis JM. Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate - interactions with frequently occurring glutamic acid residue at P2′ position of substrates. Eur J Biochem 1997;249:523-530.
10. Mahalingam B, Louis JM, Hung J, Harrison RW, Weber IT. Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. Proteins 2001;43:455-464.
11. Tie YF, Boross PI, Wang YF, Gaddis L, Liu FL, Chen XF, Tozser J, Harrison RW, Weber IT. Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 ångstrom resolution crystal structures of HIV-1 protease mutants with substrate analogs. FEBS J 2005;272:5265-5277.
12. Prabu-Jeyabalan M, Nalivaika E, Schiffer CA. How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease. J Mol Biol 2000;301:1207-1220.
13. Prabu-Jeyabalan M, Nalivaika E, Schiffer CA. Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes. Structure 2002;10:369-381.
14. Prabu-Jeyabalan M, Nalivaika EA, King NM, Schiffer CA. Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy. J Virol 2003;77:1306-1315.
15. Prabu-Jeyabalan M, Nalivaika EA, King NM, Schiffer CA. Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. J Virol 2004;78:12446-12454.
16. King NM, Prabu-Jeyabalan M, Nalivaika EA, Wigerinck P, de Bethune MP, Schiffer CA. Structural and thermodynamic basis for the binding of TMC114, a next-generation human immunodeficiency virus type 1 protease inhibitor. J Virol 2004;78:12012-12021.
17. King NM, Prabu-Jeyabalan M, Nalivaika EA, Schiffer CA. Combating susceptibility to drug resistance: lessons from HIV-1 protease. Chem Biol 2004;11:1333-1338.
18. Tuske S, Sarafianos SG, Clark AD, Ding JP, Naeger LK, White KL, Miller MD, Gibbs CS, Boyer PL, Clark P, Wang G, Gaffney BL, Jones RA, Jerina DM, Hughes SH, Arnold E. Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir. Nat Struct Mol Biol 2004;11:469-474.
19. Kirkpatrick P. Antiviral drugs: inside the envelope. Nat Rev Drug Discov 2004;3:100-100.
20. Bardi JS, Luque I, Freire E. Structure-based thermodynamic analysis of HIV-1 protease inhibitors. Biochemistry 1997;36:6588-6596.
21. Luque I, Todd MJ, Gomez J, Semo N, Freire E. Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis. Biochemistry 1998;37:5791-5797.
22. Velazquez-Campoy A, Todd MJ, Freire E. HIV-1 protease inhibitors: enthalpic versus entropic optimization of the binding affinity. Biochemistry 2000;39:2201-2207.
23. Hyland LJ, Tomaszek TA, Meek TD. Human immunodeficiency virus-1 protease. 2. Use of pH rate studies and solvent kinetic isotope effects to elucidate details of chemical mechanism. Biochemistry 1991;30:8454-8463.
24. Yamazaki T, Nicholson LK, Torchia DA, Wingfield P, Stahl SJ, Kaufman JD, Eyermann CJ, Hodge CN, Lam PYS, Ru Y, Jadhav PK, Chang CH, Weber PC. NMR and X-ray evidence that the HIV protease catalytic aspartyl groups are protonated in the complex formed by the protease and a nonpeptide cyclic urea-based inhibitor. J Am Chem Soc 1994;116:10791-10792.
25. Trylska J, Antosiewicz J, Geller M, Hodge CN, Klabe RM, Head MS, Gilson MK. Thermodynamic linkage between the binding of protons and inhibitors to HIV-1 protease. Protein Sci 1999;8:180-195.
26. Lee L-P, Tidor B. Optimization of electrostatic binding free energy. J Chem Phys 1997;106:8681-8690.
27. Lee L-P, Tidor B. Optimization of binding electrostatics: Charge complementarity in the barnase-barstar protein complex. Protein Sci 2001;10:362-377.
28. Lee L-P, Tidor B. Barstar is electrostatically optimized for tight binding to barnase. Nat Struct Biol 2001;8:73-76.
29. Sulea T, Purisima EO. Optimizing ligand charges for maximum binding affinity: a solvated interaction energy approach. J Phys Chem B 2001;105:889-899.
30. Kangas E, Tidor B. Optimizing electrostatic affinity in ligand-receptor binding: theory, computation, and ligand properties. J Chem Phys 1998;109:7522-7545.
31. Kangas E, Tidor B. Charge optimization leads to favorable electrostatic binding free energy. Phys Rev E 1999;59:5958-5961.
32. Kangas E, Tidor B. Electrostatic specificity in molecular ligand design. J Chem Phys 2000;112:9120-9131.
33. Kangas E, Tidor B. Electrostatic complementarity at ligand binding sites: application to chorismate mutase. J Phys Chem B 2001;105:880-888.
34. Green DF, Tidor B. Escherichia coli glutaminyl-tRNA synthetase is electrostatically optimized for binding of its cognate substrates. J Mol Biol 2004;342:435-452.
35. Sims PA, Wong CF, McCammon JA. Charge optimization of the interface between protein kinases and their ligands. J Comput Chem 2004;25:1416-1429.
36. Green DF, Tidor B. Design of improved protein inhibitors of HIV-1 cell entry: optimization of electrostatic interactions at the binding interface. Proteins 2005;60:644-657.
37. Gilson MK. Sensitivity analysis and charge-optimization for flexible ligands: applicability to lead optimization. J Chem Theory Comput 2006;2:259-270.
38. Dahiyat BI, Mayo SL. Protein design automation. Protein Sci 1996;5:895-903.
39. Street AG, Mayo SL. Computational protein design. Struct Fold Des 1999;7:R105-R109.
40. Saven JG. Combinatorial protein design. Curr Opin Struct Biol 2002;12:453-458.
41. Dahiyat BI, Sarisky CA, Mayo SL. De novo protein design: towards fully automated sequence selection. J Mol Biol 1997;273:789-796.
42. Dantas G, Kuhlman B, Callender D, Wong M, Baker D. A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins. J Mol Biol 2003;332:449-460.
43. Harbury PB, Plecs JJ, Tidor B, Alber T, Kim PS. High-resolution protein design with backbone freedom. Science 1998;282:1462-1467.
44. Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D. Design of a novel globular protein fold with atomic-level accuracy. Science 2003;302:1364-1368.
45. Kuhlman B, O'Neill JW, Kim DE, Zhang KYJ, Baker D. Conversion of monomeric protein L to an obligate dimer by computational protein design. Proc. Natl Acad Sci USA 2001;98:10687-10691.
46. Shifman JM, Mayo SL. Modulating calmodulin binding specificity through computational protein design. J Mol Biol 2002;323:417-423.
47. Havranek JJ, Harbury PB. Automated design of specificity in molecular recognition. Nat Struct Biol 2003;10:45-52.
48. Looger LL, Dwyer MA, Smith JJ, Hellinga HW. Computational design of receptor and sensor proteins with novel functions. Nature 2003;423:185-190.
49. Joachimiak LA, Kortemme T, Stoddard BL, Baker D. Computational design of a new hydrogen bond network and at least a 300-fold specificity switch at a protein-protein interface. J Mol Biol 2006;361:195-208.
50. Desmet J, Demaeyer M, Hazes B, Lasters I. The dead-end elimination theorem and its use in protein side-chain positioning. Nature 1992;356:539-542.
51. Leach AR, Lemon AP. Exploring the conformational space of protein side chains using dead-end elimination and the A* algorithm. Proteins 1998;33:227-239.
52. Pierce NA, Spriet JA, Desmet J, Mayo SL. Conformational splitting: A more powerful criterion for dead-end elimination. J Comput Chem 2000;21:999-1009.
53. Gordon DB, Hom GK, Mayo SL, Pierce NA. Exact rotamer optimization for protein design. J Comput Chem 2003;24:232-243.
54. Humphrey W, Dalke A, Schulten K. VMD - Visual Molecular Dynamics. J Mol Graphics 1996;14:33-38.
55. Merritt EA, Bacon DJ. Raster3D: photorealistic molecular graphics. Meth Enzymol 1997;277:505-524.
56. Nicholls A, Sharp KA, Honig B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 1991;11:281-296.
57. Ferrin TE, Huang CC, Jarvis LE, Langridge R. The MIDAS display system. J Mol Graphics 1988;6:13-27.
58. Brünger AT, Karplus M. Polar hydrogen positions in proteins: empirical energy placement and neutron-diffraction comparison. Proteins 1988;4:148-156.
59. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M. CHARMM: a program for macromolecular energy minimization and dynamics calculations. J Comput Chem 1983;4:187-217.
60. MacKerell Jr AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, III, WER, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 1998;102:3586-3616.
61. Gilson MK, Honig B. Calculation of the total electrostatic energy of a macromolecular system: solvation energies binding energies and conformational analysis. Proteins 1988;4:7-18.
62. Gilson MK, Sharp KA, Honig BH. Calculating the electrostatic potential of molecules in solution: method and error assessment. J Comput Chem 1988;9:327-335.
63. Sharp KA, Honig B. Calculating total electrostatic energies with the nonlinear Poisson-Boltzmann equation. J Phys Chem 1990;94:7684-7692.
64. Sharp KA, Honig B. Electrostatic interactions in macromolecules: theory and applications. Ann Rev Biophys Biophys Chem 1990;19:301-332.
65. Sitkoff D, Sharp KA, Honig B. Accurate calculation of hydration free-energies using macroscopic solvent models. J Phys Chem 1994;98:1978-1988.
66. Neria E, Fischer S, Karplus M. Simulation of activation free energies in molecular systems. J Chem Phys 1996;105:1902-1921.
67. Reiher WE, III. Theoretical studies of hydrogen bonding, PhD thesis Harvard University Cambridge MA, USA, 1985.
68. Vanderbei RJ. LOQO: an interior point code for quadratic programming. Optim Method Softw 1999;11-12:451-484.
69. Vanderbei RJ. LOQO User's Manual-version 3.10. Optim Method Softw 1999;11-12:485-514.
70. Dunbrack RL, Karplus M. Conformational-analysis of the backbone-dependent rotamer preferences of protein side-chains. Nat Struct Biol 1994;1:334-340.
71. Scholtz JM, Baldwin RL. The mechanism of alpha-helix formation by peptides. Ann Rev Biophys Biomol Struct 1992;21:95-118.
72. Weiner SJ, Kollman PA, Case DA, Singh UC, Ghio C, Alagona G, Profeta S, Weiner P. A new force-field for molecular mechanical simulation of nucleic-acids and proteins. J Am Chem Soc 1984;106:765-784.
73. Hui JO, Tomasselli AG, Reardon IM, Lull JM, Brunner DP, Tomich CSC, Heinrikson RL. Large-scale purification and refolding of HIV-1 protease from Escherichia coli inclusion bodies. J Protein Chem 1993;12:323-327.
74. Minor W. XDISPLAYF program. West Layfayette Indiana: Purdue University; 1993.
75. Otwinowski Z. Oscillation data reduction program. In CCP4 study weekend: data collection and processing, 29-30 Jan 1993, SERC Daresbury Laboratory, England, 1993.
76. Bailey S. The suite: programs for protein crystallography. Acta Crystallogr D 1994;50:760-763.
77. Navaza J. AMoRe: an automated package for molecular replacement. Acta Crystallogr A 1994;50:157-163.
78. Morris RJ, Perrakis A, Lamzin VS. ARP/wARP's model-building algorithms. I. The main chain. Acta Crystallogr D 2002;58:968-975.
79. Jones TA, Bergdoll M, Kjeldgaard MO. A macromolecular modeling environment. In: Bugg C, Ealick S, editors. Crystallographic and modeling methods in molecular design. Berlin: Springer-Verlag, 1990. pp 189-195.
80. Murshudov GN, Vagin AA, Dodson EJ. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D 1997;53:240-255.
81. Kuriyan J, Weis WI. Rigid protein motion as a model for crystallographic temperature factors. Proc Natl Acad Sci USA 1991;88:2773-2777.
82. Schomaker V, Trueblood KN. On the rigid-body motion of molecules in crystals. Acta Crystallogr B 1968;24:63-76.
83. Tickle IJ, Moss DS. Modelling rigid-body thermal motions in macromolecular crystal structure refinement. In IUCr99 Computing School, IUCr London, 1999.
84. Laskowski RA, Macarthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Cryst 1993;26:283-291.
85. Martin ACR. http://www.bioinf.org.uk/software/profit/.