Novel quantitative structure-activity studies of HIV-1 protease inhibitors of the cyclic urea type using descriptors derived from molecular dynamics and molecular orbital calculations

Current Computer-Aided Drug Design

Volumn 5, Issue 1, 2009, Pages 38-55

  Yoshida, Tatsusada ^a   Fujita, Toshio ^b   Chuman, Hiroshi ^a,a  

^a UNIVERSITY OF TOKUSHIMA   (Japan)

^b KYOTO UNIVERSITY   (Japan)

Author keywords

Ab initio fragment molecular orbital (FMO); Accessible surface area (ASA); Charge transfer; Cyclic urea type inhibitor (CUI); HIV 1 protease (HIV 1 PR); Inter fragment interaction energy (IFIE); Molecular dynamics (MD); Quantitative structure activity relationship (QSAR)

Indexed keywords

AMINO ACIDS; CALCULATIONS; COMPUTATIONAL CHEMISTRY; DISEASES; ELECTRONIC STRUCTURE; ENZYMES; METABOLISM; MOLECULAR DYNAMICS; MOLECULAR ORBITALS; ORBITAL CALCULATIONS; UREA; VIRUSES;

AB INITIO; AB INITIO FRAGMENT MOLECULAR ORBITAL; ACCESSIBLE SURFACE AREA; ACCESSIBLE SURFACE AREAS; CYCLIC UREA TYPE INHIBITOR; CYCLIC UREAS; FRAGMENT INTERACTION; FRAGMENT MOLECULAR ORBITAL; HIV-1 PROTEASE; HIV-1 PROTEASE (HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE); HUMAN IMMUNODEFICIENCY VIRUS; INTER-FRAGMENT INTERACTION ENERGY; INTERACTION ENERGIES; MOLECULAR DYNAMIC; QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

CHARGE TRANSFER;

4,7 DIBENZYL 2,3,4,5,6,7 HEXAHYDRO 5,6 DIHYDROXY 1,3 BIS[4 (HYDROXYMETHYL)BENZYL] 2H 1,3 DIAZEPIN 2 ONE; AMINO ACID; ANTIRETROVIRUS AGENT; CYANOIMINE DERIVATIVE; INDINAVIR; MOZENAVIR; PROTEINASE; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; UNCLASSIFIED DRUG;

AB INITIO CALCULATION; ACCURACY; ACQUIRED IMMUNE DEFICIENCY SYNDROME; COMPLEX FORMATION; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG SOLUBILITY; DRUG STRUCTURE; ENZYME BINDING; ENZYME INHIBITION; ENZYME STRUCTURE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MATHEMATICAL COMPUTING; MOLECULAR DYNAMICS; NONHUMAN; PHYSICAL CHEMISTRY; PROTEIN CONFORMATION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RELIABILITY; REVIEW; SIMULATION; VIRUS REPLICATION;

EID: 65649135842     PISSN: 15734099     EISSN: None     Source Type: Journal    
DOI: 10.2174/157340909787580845     Document Type: Review

References (108)

1. Gallo, R.C.; Sarin, P.S.; Gelmann, E.P.; Robert-Guroff, M; Richardson, E.; Kalyanaraman, V.S.; Mann, D.; Sidhu, G.D.; Stahl, R.E.; Zolla-Pazner, S.; Leibowitch, J.; Popovic, M. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science, 1983, 220, 865-876.
2. Barre-Sinoussi, F.; Chermann, J.C.; Rey, F.; Nugeyre, M.T.; Chamaret, S.; Gruest, J.; Dauguet, C.; Axler-Blin, C.; Vezinet-Brun, F.; Rouzioux, C.; Rozenbaum, W.; Montagnier, L. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science, 1983, 220, 868-871.
3. Kohl, N.E.; Emini, E.A.; Schleif, W.A.; Davis, L.J.; Heimbach, J.C.; Dixon, R.A.F.; Scolnick, E.M.; Sigal, I.S. Active human immunodeficiency virus protease is required for viral infectivity immunodeficiency. Proc. Natl. Acad. Sci. USA, 1988, 85, 4686-4690.
4. Applet, K. Crystal structures of HIV-1 protease-inhibitor complexes. Perspect. Drug Discov. Des., 1993, 1, 23-48.
5. Erickson, J.W. Design and structure of symmetry-based inhibitors of HIV-1 protease. Perspect. Drug Discov. Des., 1993, 1, 109-128.
6. Huff, J.R. Discovery and clinical development of HIV-1 protease inhibitors. Adv. Protein Chem., 2001, 56, 213-251.
7. Flexner, C. HIV drug development: The next 25 years. Nat. Rev. Drug Discov., 2007, 6, 959-964.
8. Emmelkamp J.M.; Rockstroh, J.K. CCR5 antagonists: Comparison of efficacy, side effects, pharmacokinetics and interactions-review of the literature. Eur. J. Med. Res., 2007, 12, 409-417.
9. Deeks, S.G.; Kar, S.; Gubernick, S.I.; Kirkpatrick, P. News and analysis; Raltegravir. Nat. Rev. Drug Discov., 2008, 7, 117-118.
10. Lam, P.Y.S.; Ru, Y.; Jadhav, P.K.; Aldrich, P.E.; DeLucca, G.V.; Eyermann, C.J.; Chang, C.H.; Emmett, G.; Holler, E.R.; Daneker, W.F.; Li, L.; Confalone, P.N.; McHugh, R.J.; Han, Q.; Li, R.; Markwalder, J.A.; Seitz, S.P.; Sharpe, T.R.; Bacheler, L.T.; Rayner, M.M.; Klabe, R.M.; Shum, L.; Winslow, D.L.; Kornhauser, D.M.; Jackson, D.A.; Viitanen, S.E.; Hodge C.N. Cyclic HIV protease inhibitors: Synthesis, conformational analysis, P2/P2′ structure-activity relationship, and molecular recognition of cyclic ureas. J. Med. Chem., 1996, 39, 3514-3525.
11. Navia, M.A.; Fitzgerald, P.M.; McKeever, B.M.; Leu, C.T.; Heimbach, J.C.; Herber, W.K.; Sigal, I.S.; Darke, P.L.; Springer, J.P. Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1. Nature, 1989, 337, 615-620.
12. Wlodawer, A.; Miller, M.; Jaskolski, M.; Sathyanarayana, B.K.; Baldwin, E.; Weber, I.T.; Selk, L.M.; Clawson, L.; Schneider, J.; Kent, S.B. Conserved folding in retroviral proteases: Crystal structure of a synthetic HIV-1 protease. Science, 1989, 245, 616-621.
13. Lapatto, R.; Blundell, T.; Hemmings, A.; Overington, J.; Wilderspin, A.; Wood, S.; Merson, J.R.; Whittle, P.J.; Danley, D.E.; Geoghegan, K.F.; Hawrylik, S.J.; Lee, S.E.; Scheld, K.G.; Hobart, P.M. X-ray analysis of HIV-1 proteinase at 2.7 Å resolution confirms structural homology among retroviral enzymes. Nature, 1989, 342, 299-302.
14. Brik, A.; Wong, C.-H. HIV-1 protease: Mechanism and drug discovery. Org. Biomol. Chem., 2003, 1, 5-14.
15. Das, A.; Prashar, V.; Mahale, S.; Serre, L.; Ferrer, J.L.; Hosur, M.V. Crystal structure of HIV-1 protease in situ product complex and observation of a low-barrier hydrogen bond between catalytic aspartates. Proc. Natl. Acad. Sci. USA, 2006, 103, 18464-18469.
16. Babine, R.E.; Bender, S.L. Molecular recognition of protein-ligand complexes: Applications to drug design. Chem. Rev., 1997, 97, 1359-1472.
17. Morse, G.D.; Catanzaro, L.M.; Acosta, E.P. Clinical pharmacodynamics of HIV-1 protease inhibitors: Use of inhibitory quotients to optimise pharmacotherapy. Lancet Infect. Dis., 2006, 6, 215-225.
18. Lam, P.Y.; Jadhav, P.K.; Eyermann, C.J.; Hodge, C.N.; Ru, Y.; Bacheler, L.T.; Meek, J.L.; Otto, M.J.; Rayner, M.M.; Wong, Y.N.; Chang, C.H.; Weber, P.C.; Jackson, D.A.; Sharpe, T.R.; Viitanen, S.E. Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science, 1994, 263, 380-384.
19. De Lucca, G.V.; Viitanen, S.E.; Lam, P.Y.S. Cyclic HIV protease inhibitors capable of displacing the active site structural water molecule. Drug Discov. Today, 1997, 2, 6-18.
20. Roberts, N.A.; Martin, J.A.; Kinchington, D.; Broadhurst, A.V.; Craig, J.C.; Duncan, I.B.; Galpin, S.A.; Handa, B.K.; Kay, J.; Kröhn, A.; Lambert, R.W.; Merrett, J.H.; Mills, J.S.; Parkes, K.E.B.; Redshaw, S.; Ritchie, A.J.; Taylor, D.L.; Thomas, G.J.; Machin, P.J. Rational design of peptide-based HIV proteinase inhibitors. Science, 1990, 248, 358-361.
21. Dorsey, B.D.; Levin, R.B.; McDaniel, S.L.; Vacca, J.P.; Guare, J.P.; Darke, P.L.; Zugay, J.A.; Emini, E.A.; Schleif, W.A.; Quintero, J.C.; Lin, J.H.; Chen, I.W.; Holloway, M.K.; Fitzgerald, P.M.D.; Axel, M.G.; Ostovic, D.; Anderson, P.S.; Huf, J.R. L-735, 524: The design of a potent and orally bioavailable HIV protease inhibitor. J. Med. Chem., 1994, 37, 3443-3451.
22. Kempf, D.J.; Sham, H.L.; Marsh, K.C.; Flentge, C.A.; Betebenner, D.; Green, B.E.; McDonald, E.; Vasavanonda, S.; Saldivar, A.; Wideburg, N.E.; Kati, W.M.; Ruiz, L.; Zhao, C.; Fino, L.; Patterson, J.; Molla, A.; Plattner, J.J.; Norbeck, D.W. Discovery of ritonavir, a potent inhibitor of HIV protease with high oral bioavailability and clinical efficacy. J. Med. Chem., 1998, 41, 602-617.
23. Jadhav, P.K.; Woerner, F.J.; Lam, P.Y.S.; Hodge, C.N.; Eyermann, C.J.; Man, H.-W.; Daneker, W.F.; Bacheler, L.T.; Rayner, M.M.; Meek, J.L.; Erickson-Viitanen, S.; Jackson, D.A.; Calabrese, J.C.; Schadt, M.; Chang, C.-H. Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: Synthesis, structure-activity relationships, and X-ray crystal structure studies. J. Med. Chem., 1998, 41, 1446-1455.
24. Tucker, T.J.; Lumma, W.C., Jr.; Payne, L.S.; Wai, J.M.; De Solms, S.J.; Giuliani, E.A.; Darke, P.L.; Heimbach, J.C.; Zugay, J.A.; Schleif, W.A.; Quintero, J.C.; Emini, E.A.; Huff, J.R.; Anderson, P.S. A series of potent HIV-1 protease inhibitors containing a hydroxyethyl secondary amine transition state isostere: Synthesis, enzyme inhibition, and antiviral activity. J. Med. Chem., 1992, 35, 2525-2533.
25. Nugiel, D.A.; Jacobs, K.; Kaltenbach, R.F.; Worley, T.; Patel, M.; Meyer, D.T.; Jadhav, P.K.; De Lucca, G.V.; Smyser, T.E.; Klabe, R.M.; Bacheler, L.T.; Rayner, M.M.; Seitz, S.P. Preparation and structure-activity relationship of novel P1/P1′-substituted cyclic urea-based human immunodeficiency virus type-1 protease inhibitors. J. Med. Chem., 1996, 39, 2156-2169.
26. Romines, K.R.; Morris, J.K.; Howe, W.J.; Tomich, P.K.; Horng, M.M.; Chong, K.T.; Hinshaw, R.R.; Anderson, D.J.; Strohbach, J.W.; Turner, S.R.; Mizsak, S.A. Cycloalkylpyranones and cycloalkyldihydropyrones as HIV protease inhibitors: Exploring the impact of ring size on structure-activity relationships. J. Med. Chem., 1996, 39, 4125-4130.
27. De Lucca, G.V.; Liang, J.; De Lucca, I. Stereospecific synthesis, structure-activity relationship, and oral bioavailability of tetrahydropyrimidin-2-one HIV protease inhibitors. J. Med. Chem., 1999, 42, 135-152.
28. Boyer, F.E.; Vara Prasad, J.V.; Domagala, J.M.; Ellsworth, E.L.; Gajda, C.; Hagen, S.E.; Markoski, L.J.; Tait, B.D.; Lunney, E.A.; Palovsky, A.; Ferguson, D.; Graham, N.; Holler, T.; Hupe, D.; Nouhan, C.; Tummino, P.J.; Urumov, A.; Zeikus, E.; Zeikus, G.; Gracheck, S.J.; Sanders, J.M.; VanderRoest S.; Brodfuehrer, J.; Iyer, K.; Sinz, M.; Gulnik, S.V. 5,6-Dihydropyran-2-ones possessing various sulfonyl functionalities: potent nonpeptidic inhibitors of HIV protease. J. Med. Chem., 2000, 43, 843-858.
29. Myers, A.G.; Barbay, J.K.; Zhong, B. Asymmetric synthesis of chiral organofluorine compounds: Use of nonracemic fluoroio-doacetic acid as a practical electrophile and its application to the synthesis of monofluoro hydroxyethylene dipeptide isosteres within a novel series of HIV protease inhibitors. J. Am. Chem. Soc., 2001, 123, 7207-7219.
30. Mühlman, A.; Classon, B.; Hallberg, A.; Samuelsson, B. Synthesis of potent C(2)-symmetric, diol-based hiv-1 protease inhibitors. Investigation of thioalkyl and thioaryl P1/P1′ substituents. J. Med. Chem., 2001, 44, 3402-3406.
31. Chen, X.; Kempf, D.J.; Li, L.; Sham, H.L.; Vasavanonda, S.; Wideburg, N.E.; Saldivar, A.; Marsh, K.C.; McDonald, E.; Norbeck, D.W. Synthesis and SAR studies of potent HIV protease inhibitors containing novel dimethylphenoxyl acetates as P2 ligands. Bioorg. Med. Chem. Lett., 2003, 13, 3657-3660.
32. Surleraux, D.L.; Tahri, A.; Verschueren, W.G.; Pille, G.M.; de Kock, H.A.; Jonckers, T.H.; Peeters, A.; De Meyer S, Azijn, H.; Pauwels, R.; de Bethune, M.P.; King, N. M.; Prabu-Jeyabalan, M.; Schiffer, C.A.; Wigerinck, P.B. Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor. J. Med. Chem., 2005, 48, 1813-1822.
33. Blum, A.; Böttcher, J.; Heine, A.; Klebe, G.; Diederich, W.E. Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a pyrrolidine scaffold. J. Med. Chem., 2008, 51, 2078-2087.
34. Garg, R.; Gupta, S.P.; Gao, H.; Babu, M.S.; Debnath, A.K.; Hansch, C. Comparative quantitative structure-activity relationship studies on anti-HIV drugs. Chem. Rev., 1999, 99, 3525-3601.
35. Kurup, A.; Babu, M.S.; Garg, R.; Hansch, C. HIV-1 protease inhibitors: A comparative QSAR analysis. Curr. Med. Chem., 2003, 10, 1679-1688.
36. Garg, R.; Bhhatarai, B. A mechanistic study of 3-aminoindazole cyclic urea HIV-1 protease inhibitors using comparative QSAR. Bioorg. Med. Chem., 2004, 12, 5819-5831.
37. Kellog, G.E.; Semus, S.; Abraham, D. HINT: A new method of empirical hydrophobic field calculation for CoMFA. J. Comput.-Aided Mol. Des., 1991, 5, 545-552.
38. Debnath, A.K. Three-dimensional quantitative structure-activity relationship study on cyclic urea derivatives as HIV-1 protease inhibitors: Application of comparative molecular field analysis. J. Med. Chem., 1999, 42, 249-259.
39. Jayatilleke, P.N.; Nair, A.C.; Zauhar, R.; Welsh, W.J. Computational studies on HIV-1 protease inhibitors: Influence of calculated inhibitor-enzyme binding affinities on the statistical quality of 3D-QSAR CoMFA models. J. Med. Chem., 2000, 43, 4446-4451.
40. Schaal, W.; Karlsson, A.; Ahlsén, G.; Lindberg, J.; Andersson, H.O.; Danielson, U.H.; Classon, B.; Unge, T.; Samuelsson, B.; Hultén, J.; Hallberg, A.; Karlén, A. Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors. J. Med. Chem., 2001, 44, 155-169.
41. Nair, A.C.; Jayatilleke, P.; Wang, X.; Miertus, S.; Welsh, W.J. Computational studies on tetrahydropyrimidine-2-one HIV-1 protease inhibitors: Improving three-dimensional quantitative structure-activity relationship comparative molecular field analysis models by inclusion of calculated inhibitor- and receptor-based properties. J. Med. Chem., 2002, 45, 973-983.
42. Avram, S.; Svab, L.; Bologa, C.; Flonta, M.-L. Correlation between the predicted and the observed biological activity of the symmetric and nonsymmetric cyclic urea derivatives used as HIV-1 protease inhibitors. A 3D-QSAR-CoMFA method for new antiviral drug design. J. Cell. Mol. Med., 2003, 7, 287-296.
43. Tervo, A.J.; Nyrönen, T.H.; Rönkkö, T.; Poso, A. Comparing the quality and productiveness between 3D QSAR models obtained from manual and automated alignment. J. Chem. Inf. Sci., 2004, 44, 807-816.
44. Fernández, M.; Caballero, J. Modeling of activity of cyclic urea HIV-1 protease inhibitors using regularized-artificial neural networks. Bioorg. Med. Chem., 2006, 14, 280-294.
45. Milac, A.-L.; Avram, S.; Petrescu, A.-J. Evaluation of a neural networks QSAR method based on ligand representation using substituent descriptors: Application to HIV-1 protease inhibitors. J. Mol. Graph. Model., 2006, 25, 37-45.
46. Fedorov, D.G.; Kitaura, K. In Modern Methods for Theoretical Physical Chemistry of Biopolymers; Starikov, E.B., Lewis, J.P., Tanaka, S., Eds.; Elsevier: Amsterdam, 2006, pp. 3-38.
47. Wilkerson, W.W.; Akamike, E.; Cheatham, W.W.; Hollis, A.Y.; Collins, R.D.; DeLucca, I.; Lam, P.Y.S.; Ru, Y. HIV protease inhibitory bis-benzamide cyclic ureas: A quantitative structure-activity relationship analysis. J. Med. Chem., 1996, 39, 4299-4312.
48. McCammon, J.A.; Harvey, S.C. In Dynamics of Proteins and Nucleic Acids; Cambridge University Press: Cambridge, 1987, pp. 1-34,
49. Scott, W.R.P.; Schiffer, C.A. Curling of flap tips in HIV-1 protease as a mechanism for substrate entry and tolerance of drug resistance. Structure, 2000, 8, 1259-1265.
50. Meagher, K.L.; Carlson, H.A. Solvation influences flap collapse in HIV-1 protease. Proteins, 2005, 58, 119-125.
51. Hamelberg, D.; McCammon, J.A. Fast peptidyl cis-trans isomerization within the flexible Gly-rich flaps of HIV-1 protease. J. Am. Chem. Soc., 2005, 127, 13778-13779.
52. Hornak, V.; Okur, A.; Rizzo, R.C.; 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, 2812-2813.
53. Toth, G.; Borics, A. Closing of the flaps of HIV-1 protease induced by substrate binding: A model of a flap closing mechanism in retroviral aspartic proteases. Biochemistry, 2006, 45, 6606-6614.
54. Hornak, V.; Simmerling, C. Targeting structural flexibility in HIV-1 protease inhibitor binding. Drug Discov. Today, 2007, 12, 132-138.
55. Ode, H.; Neya, S.; Hata, M.; Sugiura, W.; Hoshino, T. Computational simulations of HIV-1 proteases-multi-drug resistance due to nonactive site mutation L90M. J. Am. Chem. Soc., 2006, 128, 7887-7895.
56. Hyland, L.J.; Tomaszek, T.A.; Meek, T.D. 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.
57. Yamazaki, T.; Nicholson, L.K.; Torchia, D.A.; Wingfield, P.; Stahl, S.J.; Kaufman, J.D.; Eyermann, C.J.; Hodge, C.N.; Lam, P.Y.S.; Ru, Y.; Jadhav, P.K.; Chang, C.H.; Weber, P.C. NMR and X-ray evidence that the HIV protease catalytic aspartyl groups are protonated in the complex formed by the protease and a non-peptide cyclic urea-based inhibitor. J. Am. Chem. Soc., 1994, 116, 10791-10792.
58. Smith, R.; Brereton, I.M.; Chai, R.Y.; Kent, S.B. Ionization states of the catalytic residues in HIV-1 protease. Nat. Struct. Biol., 1996, 3, 946-950.
59. Tropsha, A.; Hermans, J. Application of free energy simulations to the binding of a transition-state-analogue inhibitor to HTV protease. Protein Eng., 1992, 5, 29-33.
60. Wang, L.; Duan, Y.; Stouten, P.; Lucca, G.V.D.; Klabe, R.M.; Kollman, P.A. Does a diol cyclic urea inhibitor of HIV-1 protease bind tighter than its corresponding alcohol form? A study by free energy perturbation and continuum electrostatics calculations. J. Comput.-Aided Mol. Des., 2001, 15, 145-156.
61. Piana, S.; Sebastiani, D.; Carloni, P.; Parrinello, M. Ab initio molecular dynamics-based assignment of the protonation state of pepstatin A/HIV-1 protease cleavage site. J. Am. Chem. Soc., 2001, 123, 8730-8737.
62. Mardis, K.L.; Luo, R.; Gilson, M.K. Interpreting trends in the binding of cyclic ureas to HIV-1 protease. J. Mol. Biol., 2001, 309, 507-517.
63. Piana, S.; Carloni, P.; Parrinello, M. Role of conformational fluctuations in the enzymatic reaction of HIV-1 protease. J. Mol. Biol., 2002, 319, 567-583.
64. Carloni, P. Density functional theory-based molecular dynamics of biological systems. Quant. Struct.-Act. Relat., 2002, 21, 166-172.
65. Sirois, S.; Proynov, E.I.; Truchon, J.F.; Tsoukas, C.M.; Salahub, D.R. A density functional study of the hydrogen-bond network within the HIV-1 protease catalytic site cleft. J. Comput. Chem., 2003, 24, 1110-1119.
66. Piana, S.; Bucher, D.; Carloni, P.; Rothlisberger, U. Reaction mechanism of HIV-1 protease by hybrid Car-Parrinello/classical MD simulations. J. Phys. Chem. B, 2004, 108, 11139-11149.
67. Ode, H.; Neya, S.; Hata, M.; Sugiura, W.; Hoshino, T. Computational simulations of HIV-1 proteases-multi-drug resistance due to nonactive site mutation L90M. J. Am. Chem. Soc., 2006, 128, 7887-7895.
68. Aruksakunwong, O.; Wittayanarakul, K.; Sompornpisut, P.; Sanghiran, V.; Parasuk, V.; Hannongbua, S. Structural and dynamical properties of different protonated states of mutant HIV-1 protease complexed with the saquinavir inhibitor studied by molecular dynamics simulations. J. Mol. Graphics Modell., 2006, 25, 324-332.
69. Suguna, K.; Padlan, E.A.; Smith, C.W.; Carlson, W.D.; Davies, D.R. Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: Implications for a mechanism of action. Proc. Natl. Acad. Sci. USA, 1987, 84, 7009-7013.
70. Northrop, D.B. Follow the protons: A low-barrier hydrogen bond unifies the mechanisms of the aspartic proteases. Acc. Chem. Res., 2001, 34, 790-797.
71. Case, D.A.; Cheatham, T.E. III; Darden, T.; Gohlke, H.; Luo, R.; Merz, K.M. Jr.; Onufriev, A.; Simmerling, C.; Wang, B.; Woods, R.J. The Amber biomolecular simulation programs. J. Comput. Chem., 2005, 26, 1668-1688.
72. Bayly, C.I.; Cieplak, P.; Cornell, W.D.; Kollman, P.A. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model. J. Phys. Chem., 1993, 97, 10269-10280.
73. Yoshida, T.; Yamagishi, K.; Chuman, H. QSAR study of cyclic urea type HIV-1 PR inhibitors using ab initio MO calculation of their complex structures with HIV-1 PR. QSAR Comb. Sci., 2008, 27, 694-703.
74. Fukuzawa, K.; Kitaura, K.; Nakata, K.; Nakano, T. Fragment molecular orbital study of the binding energy of ligands to the estrogen receptor. Pure Appl. Chem., 2003, 75, 2405-2410.
75. Fukuzawa, K.; Kitaura, K.; Uebayashi, M.; Nakata, K.; Kaminuma, T.; Nakano, T. Ab initio quantum mechanical study of the binding energies of human estrogen receptor α with its ligands: An application of fragment molecular orbital method. J. Comp. Chem., 2005, 26, 1-10.
76. Fukuzawa, K.; Komeiji, Y.; Mochizuki, Y.; Kato, A.; Nakano, T.; Tanaka, S. Intra- and intermolecular interactions between cyclic-AMP receptor protein and DNA: Ab initio fragment molecular orbital study. J. Comput. Chem., 2006, 27, 948-960.
77. Fukuzawa, K.; Mochizuki, Y.; Tanaka, S.; Kitaura, K.; Nakano, T. Molecular interactions between estrogen receptor and its ligand studied by the ab initio fragment molecular orbital method. J. Phys. Chem. B, 2006, 110, 16102-16110.
78. Yamagishi, K.; Yamamoto, K.; Yamada, S.; Tokiwa, H. Functions of key residues in the ligand-binding pocket of vitamin D receptor: Fragment molecular orbital-interfragment interaction energy analysis. Chem. Phys. Lett., 2006, 420, 465-468.
79. Sawada, T.; Hashimoto, T.; Nakano, H.; Suzuki, T.; Ishida, H.; Kiso, M. Why does avian influenza A virus hemagglutinin bind to avian receptor stronger than to human receptor? Ab initio fragment molecular orbital studies. Biochem. Biophys. Res. Commun., 2006, 351, 40-43.
80. Ito, M.; Fukuzawa, K.; Mochizuki, Y.; Nakano, T.; Tanaka, S. Ab initio fragment molecular orbital study of molecular interactions between liganded retinoid X receptor and its coactivator: Roles of helix 12 in the coactivator binding mechanism. J. Phys. Chem. B, 2007, 111, 3525-3533.
81. Sawada, T.; Hashimoto, T.; Nakano, H.; Suzuki, T.; Suzuki, Y.; Kawaoka, Y.; Ishida, H.; Kiso, M. Why does avian influenza A virus hemagglutinin bind to avian receptor stronger than to human receptor? Ab initio fragment molecular orbital studies. Biochem. Biophys. Res. Commun., 2006, 355, 6-9.
82. Watanabe, T.; Inadomi, Y.; Fukuzawa, K.; Nakano, T.; Tanaka, S.; Nilsson, L.; Nagashima, U. DNA and estrogen receptor interaction revealed by fragment molecular orbital calculations. J. Phys. Chem. B, 2007, 111, 9621-9627.
83. Watanabe, H.; Enomoto, T.; Tanaka, S. Ab initio study of molecular interactions in higher plant and Galdieria partita Rubiscos with the fragment molecular orbital method. Biochem. Biophys. Res. Commun., 2007, 361, 367-372.
84. Ito, M.; Fukuzawa, K.; Mochizuki, Y.; Nakano, T.; Tanaka, S. Ab initio fragment molecular orbital study of molecular interactions between liganded retinoid X receptor and its coactivator; part II: influence of mutations in transcriptional activation function 2 activating domain core on the molecular interactions. J. Phys. Chem. A, 2008, 112, 1986-1998.
85. Iwata, T.; Fukuzawa, K.; Nakajima, K.; Aida-Hyugaji, S.; Mochizuki, Y.; Watanabe, H.; Tanaka, S. Theoretical analysis of binding specificity of influenza viral hemagglutinin to avian and human receptors based on the fragment molecular orbital method. Comput. Biol. Chem., 2008, 32, 198-221.
86. Harada, T.; Yamagishi, K.; Nakano, T.; Kitaura, K.; Tokiwa, H. Ab initio fragment molecular orbital study of ligand binding to human progesterone receptor ligand-binding domain. Naunyn-Schmiedebergs Arch. Pharmacol., 2008, 377, 607-615.
87. Ito, M.; Fukuzawa, K.; Ishikawa, T.; Mochizuki, Y.; Nakano, T.; Tanaka, S. Ab initio fragment molecular orbital study of molecular interactions in liganded retinoid X receptor: Specification of residues associated with ligand inducible information transmission. J. Phys. Chem. B, 2008, 112, 12081-12094.
88. ABINIT-MP ver 4.1 is available from the website of RSS21 project: Http://www.ciss.iis.u-tokyo.ac.jp/rss21/
89. Tanford, C. In The Hydrophobic Effect; 2nd ed.; Wiley-Interscience: New York, 1980, pp. 5-20.
90. Chothia, C. Hydrophobic bonding and accessible surface area in proteins. Nature, 1974, 248, 338-339.
91. Eisenberg, D.; McLachlan, A.D. Solvation energy in protein folding and binding. Nature, 1986, 319, 199-203.
92. Chuman, H.; Mori, A.; Tanaka, H.; Yamagami, C.; Fujita, T. Analyses of the partition coefficient, log P, using ab initio MO parameter and accessible surface area of solute molecules. J. Pharm. Sci., 2004, 93, 2681-2697.
93. Bondi, A. van der Waals volumes and radii. J. Phys. Chem., 1964, 68, 441-451.
94. Mulliken, R.S. Electronic population analysis on LCAO-MO molecular wave functions. I. J. Chem. Phys., 1955, 23, 1833-1840.
95. Amari, S.; Aizawa, M.; Zhang, J.; Fukuzawa, K.; Mochizuki, Y.; Iwasawa, Y.; Nakata, K.; Chuman, H.; Nakano, T. VISCANA: Visualized cluster analysis of protein-ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening. J. Chem. Inf. Model., 2006, 46, 221-230.
96. BioStation Viewer ver 8.0 is available from the website of RSS21 project: Http://www.ciss.iis.u-tokyo.ac.jp/rss21/
97. Leach, A.W. In Molecular Modelling: Principles and Applications; Longman: Essex, 1996, pp. 451-453.
98. Abraham, M.H.; McGowan, J.C. The use of characteristic volumes to measure cavity terms in reversed phase liquid chromatography. Chromatographia, 1987, 23, 243-246.
99. Sharp, K. Entropy-enthalpy compensation: Fact or artifact? Protein Sci., 2001, 10, 661-667.
100. Hansch, C.; Leo. Exploring QSAR: Fundamentals and Applications in Chemistry and Biology, American Chemical Society: Washington, D.C., 1995.
101. Exner, O. In Correlation Analysis in Chemistry; Chapman, N. B.; Shorter, J. Eds.; Plenum Press: New York, 1978, pp. 439-540.
102. Fujita, T.; Nishioka, T.; Nakajima, M. Hydrogen-bonding parameter and its significance in quantitative structure-activity studies. J. Med. Chem., 1977, 20, 1071-1081.
103. Joesten, M.D.; Schaad, L.J. In Hydrogen Bonding; Marcel Dekker, Inc.: New York, 1974, pp. 291-381.
104. Gupta, S.P.; Babu, M.S.; Garg, R.; Sowmya, S. Quantitative structure-activity relationship studies on cyclic urea-based HIV protease inhibitors. J. Enz. Inhib., 1998, 13, 399-407.
105. Gupta, S.P.; Babu, M.S. Quantitative structure-activity relationship studies on cyclic cyanoguanidines acting as HIV-1 protease inhibitors. Bioorg. Med. Chem., 1999, 7, 2549-2553.
106. Gayathri, P.; Pande, V.; Sivakumarc, R.; Gupta, S.P. A quantitative structure-activity relationship study on some HIV-1 protease inhibitors using molecular connectivity index. Bioorg. Med. Chem., 2001, 9, 3059-3063.
107. Garg, R.; Patel, D. Hydrophobicity in the design of P2/P2′ tetrahydropyrimidinone HIV protease inhibitors. Bioorg. Med. Chem. Lett., 2005, 15, 3767-3770.
108. ClogP for windows ver. 4.0, BioByte Corp., 201 W. Fourth St., Suite 204, Claremot, CA 91711 USA.