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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

From Recognition to Reaction Mechanism: An Overview on the Interactions between HIV-1 Protease and its Natural Targets

Author(s): Monsurat M. Lawal, Zainab K. Sanusi, Thavendran Govender, Glenn E.M. Maguire, Bahareh Honarparvar and Hendrik G. Kruger*

Volume 27, Issue 15, 2020

Page: [2514 - 2549] Pages: 36

DOI: 10.2174/0929867325666181113122900

Price: $65

Abstract

Current investigations on the Human Immunodeficiency Virus Protease (HIV-1 PR) as a druggable target towards the treatment of AIDS require an update to facilitate further development of promising inhibitors with improved inhibitory activities. For the past two decades, up to 100 scholarly reports appeared annually on the inhibition and catalytic mechanism of HIV-1 PR. A fundamental literature review on the prerequisite of HIV-1 PR action leading to the release of the infectious virion is absent. Herein, recent advances (both computationally and experimentally) on the recognition mode and reaction mechanism of HIV-1 PR involving its natural targets are provided. This review features more than 80 articles from reputable journals. Recognition of the natural Gag and Gag-Pol cleavage junctions by this enzyme and its mutant analogs was first addressed. Thereafter, a comprehensive dissect of the enzymatic mechanism of HIV-1 PR on its natural polypeptide sequences from literature was put together. In addition, we highlighted ongoing research topics in which in silico methods could be harnessed to provide deeper insights into the catalytic mechanism of the HIV-1 protease in the presence of its natural substrates at the molecular level. Understanding the recognition and catalytic mechanism of HIV-1 PR leading to the release of an infective virion, which advertently affects the immune system, will assist in designing mechanismbased inhibitors with improved bioactivity.

Keywords: HIV-1 PR, natural substrates, recognition pattern, reaction mechanism, transition state modeling, immune system.

« Previous Next »
[1]
Park, H.; Suh, J.; Lee, S. Ab initio studies on the catalytic mechanism of aspartic proteinases: nucleophilic versus general acid/general base mechanism. J. Am. Chem. Soc., 2000, 122(16), 3901-3908.
[http://dx.doi.org/10.1021/ja992849p]
[2]
Canduri, F.; Teodoro, L.G.; Fadel, V.; Lorenzi, C.C.; Hial, V.; Gomes, R.A.; Neto, J.R.; de Azevedo, W.F., Jr Structure of human uropepsin at 2.45 A resolution. Acta Crystallogr. D Biol. Crystallogr., 2001, 57(Pt 11), 1560-1570.
[http://dx.doi.org/10.1107/S0907444901013865] [PMID: 11679720]
[3]
de Azevedo, W.F., Jr; Canduri, F.; Fadel, V.; Teodoro, L.G.; Hial, V.; Gomes, R.A. Molecular model for the binary complex of uropepsin and pepstatin. Biochem. Biophys. Res. Commun., 2001, 287(1), 277-281.
[http://dx.doi.org/10.1006/bbrc.2001.5555] [PMID: 11549287]
[4]
Koelsch, G. BACE1 function and inhibition: implications of intervention in the amyloid pathway of Alzheimer’s disease pathology. Molecules, 2017, 22(10), 1723.
[http://dx.doi.org/10.3390/molecules22101723] [PMID: 29027981]
[5]
Aufschnaiter, A.; Kohler, V.; Büttner, S. Taking out the garbage: cathepsin D and calcineurin in neurodegeneration. Neural Regen. Res., 2017, 12(11), 1776-1779.
[http://dx.doi.org/10.4103/1673-5374.219031] [PMID: 29239314]
[6]
Aufschnaiter, A.; Habernig, L.; Kohler, V.; Diessl, J.; Carmona-Gutierrez, D.; Eisenberg, T.; Keller, W.; Büttner, S. The coordinated action of calcineurin and cathepsin D protects against α-synuclein toxicity. Front. Mol. Neurosci., 2017, 10, 207.
[http://dx.doi.org/10.3389/fnmol.2017.00207] [PMID: 28713240]
[7]
Canduri, F.; Ward, R.J.; de Azevedo Júnior, W.F.; Gomes, R.A.; Arni, R.K. Purification and partial characterization of cathepsin D from porcine (Sus scrofa) liver using affinity chromatography. Biochem. Mol. Biol. Int., 1998, 45(4), 797-803.
[http://dx.doi.org/10.1080/15216549800203222] [PMID: 9713704]
[8]
Agbowuro, A.A.; Huston, W.M.; Gamble, A.B.; Tyndall, J.D.A. Proteases and protease inhibitors in infectious diseases. Med. Res. Rev., 2018, 38(4), 1295-1331.
[http://dx.doi.org/10.1002/med.21475] [PMID: 29149530]
[9]
Silva, A.M.; Lee, A.Y.; Gulnik, S.V.; Maier, P.; Collins, J.; Bhat, T.N.; Collins, P.J.; Cachau, R.E.; Luker, K.E.; Gluzman, I.Y.; Francis, S.E.; Oksman, A.; Goldberg, D.E.; Erickson, J.W. Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum. Proc. Natl. Acad. Sci. USA, 1996, 93(19), 10034-10039.
[http://dx.doi.org/10.1073/pnas.93.19.10034] [PMID: 8816746]
[10]
Garrec, J.; Sautet, P.; Fleurat-Lessard, P. Understanding the HIV-1 protease reactivity with DFT: what do we gain from recent functionals? J. Phys. Chem. B, 2011, 115(26), 8545-8558.
[http://dx.doi.org/10.1021/jp200565w] [PMID: 21667951]
[11]
Potempa, M. The triple threat of HIV-1 protease inhibitors. In: The Future of HIV-1 Therapeutics; Springer, 2015, pp. 203-241.
[12]
Lockhat, H.A.; Silva, J.R.; Alves, C.N.; Govender, T.; Lameira, J.; Maguire, G.E.; Sayed, Y.; Kruger, H.G. Binding free energy calculations of nine FDA-approved protease inhibitors against HIV-1 subtype C I36T↑T containing 100 amino acids per monomer. Chem. Biol. Drug Des., 2016, 87(4), 487-498.
[http://dx.doi.org/10.1111/cbdd.12690] [PMID: 26613568]
[13]
Maseko, S.B.; Natarajan, S.; Sharma, V.; Bhattacharyya, N.; Govender, T.; Sayed, Y.; Maguire, G.E.; Lin, J.; Kruger, H.G. Purification and characterization of naturally occurring HIV-1 (South African subtype C) protease mutants from inclusion bodies. Protein Expr. Purif., 2016, 122, 90-96.
[http://dx.doi.org/10.1016/j.pep.2016.02.013] [PMID: 26917227]
[14]
Swanstrom, R.; Wills, J. Synthesis, assembly, and processing of viral proteins; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 1997.
[15]
Debouck, C.; Gorniak, J.G.; Strickler, J.E.; Meek, T.D.; Metcalf, B.W.; Rosenberg, M. Human immunodeficiency virus protease expressed in Escherichia coli exhibits autoprocessing and specific maturation of the gag precursor. Proc. Natl. Acad. Sci. USA, 1987, 84(24), 8903-8906.
[http://dx.doi.org/10.1073/pnas.84.24.8903] [PMID: 3321060]
[16]
Darke, P.L.; Nutt, R.F.; Brady, S.F.; Garsky, V.M.; Ciccarone, T.M.; Leu, C.T.; Lumma, P.K.; Freidinger, R.M.; Veber, D.F.; Sigal, I.S. HIV-1 protease specificity of peptide cleavage is sufficient for processing of gag and pol polyproteins. Biochem. Biophys. Res. Commun., 1988, 156(1), 297-303.
[http://dx.doi.org/10.1016/S0006-291X(88)80839-8] [PMID: 3052448]
[17]
Prabu-Jeyabalan, M.; Nalivaika, E.; Schiffer, C.A. How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease. J. Mol. Biol., 2000, 301(5), 1207-1220.
[http://dx.doi.org/10.1006/jmbi.2000.4018] [PMID: 10966816]
[18]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[19]
Prabu-Jeyabalan, M.; Nalivaika, E.; Schiffer, C.A. Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes. Structure, 2002, 10(3), 369-381.
[http://dx.doi.org/10.1016/S0969-2126(02)00720-7] [PMID: 12005435]
[20]
Lv, Z.; Chu, Y.; Wang, Y. HIV protease inhibitors: a review of molecular selectivity and toxicity. HIV AIDS (Auckl.), 2015, 7, 95-104.
[PMID: 25897264]
[21]
Dunn, B.M. Structure and mechanism of the pepsin-like family of aspartic peptidases. Chem. Rev., 2002, 102(12), 4431-4458.
[http://dx.doi.org/10.1021/cr010167q] [PMID: 12475196]
[22]
Mahalingam, B.; Louis, J.M.; Hung, J.; Harrison, R.W.; Weber, I.T. Structural implications of drug-resistant mutants of HIV-1 protease: high-resolution crystal structures of the mutant protease/substrate analogue complexes. Proteins, 2001, 43(4), 455-464.
[http://dx.doi.org/10.1002/prot.1057] [PMID: 11340661]
[23]
Lee, S-K.; Potempa, M.; Kolli, M.; Özen, A.; Schiffer, C.A.; Swanstrom, R. Context surrounding processing sites is crucial in determining cleavage rate of a subset of processing sites in HIV-1 Gag and Gag-Pro-Pol polyprotein precursors by viral protease. J. Biol. Chem., 2012, 287(16), 13279-13290.
[http://dx.doi.org/10.1074/jbc.M112.339374] [PMID: 22334652]
[24]
Trylska, J. Computational Modelling of Protonation Equilibria and Reaction Mechanism of HIV-1 Protease., 2001.
[25]
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(30), 11139-11149.
[http://dx.doi.org/10.1021/jp037651c]
[26]
Altoè, P. A tunable QM/MM approach to chemical reactivity, structure and physico-chemical properties prediction. Theor. Chem. Acc., 2007, 118(1), 219-240.
[http://dx.doi.org/10.1007/s00214-007-0275-9]
[27]
Honarparvar, B.; Govender, T.; Maguire, G.E.; Soliman, M.E.; Kruger, H.G. Integrated approach to structure-based enzymatic drug design: molecular modeling, spectroscopy, and experimental bioactivity. Chem. Rev., 2014, 114(1), 493-537.
[http://dx.doi.org/10.1021/cr300314q] [PMID: 24024775]
[28]
Forli, S.; Olson, A.J. Computational challenges of structure-based approaches applied to HIV. In: The Future of HIV-1 Therapeutics; Springer, 2015, pp. 31-51.
[29]
Pintro, V.O.; de Azevedo, W.F.; Filgueira, W. Optimized virtual screening workflow: Towards target-based polynomial scoring functions for HIV-1 protease. Comb. Chem. High Throughput Screen., 2017, 20(9), 820-827.
[http://dx.doi.org/10.2174/1386207320666171121110019] [PMID: 29165067]
[30]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera--a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[31]
Gulnik, S.; Erickson, J.W.; Xie, D. HIV protease: enzyme function and drug resistance. Vitam. Horm., 2000, 58, 213-256.
[http://dx.doi.org/10.1016/S0083-6729(00)58026-1] [PMID: 10668400]
[32]
Rodríguez-Barrios, F.; Gago, F. HIV protease inhibition: limited recent progress and advances in understanding current pitfalls. Curr. Top. Med. Chem., 2004, 4(9), 991-1007.
[http://dx.doi.org/10.2174/1568026043388529] [PMID: 15134553]
[33]
Nijhuis, M.; van Maarseveen, N.M.; Boucher, C.A. HIV protease resistance and viral fitness. Curr. Opin. HIV AIDS, 2007, 2(2), 108-115.
[http://dx.doi.org/10.1097/COH.0b013e32801682f6] [PMID: 19372875]
[34]
Brik, A.; Wong, C-H. HIV-1 protease: mechanism and drug discovery. Org. Biomol. Chem., 2003, 1(1), 5-14.
[http://dx.doi.org/10.1039/b208248a] [PMID: 12929379]
[35]
Sussman, F.; Villaverde, M.C.; Domínguez, J.L.; Danielson, U.H. On the active site protonation state in aspartic proteases: implications for drug design. Curr. Pharm. Des., 2013, 19(23), 4257-4275.
[http://dx.doi.org/10.2174/1381612811319230009] [PMID: 23170891]
[36]
Deo, S.K.; Lewis, J.C.; Daunert, S. Bioluminescence detection of proteolytic bond cleavage by using recombinant aequorin. Anal. Biochem., 2000, 281(1), 87-94.
[http://dx.doi.org/10.1006/abio.2000.4539] [PMID: 10847614]
[37]
Makatini, M.M.; Petzold, K.; Arvidsson, P.I.; Honarparvar, B.; Govender, T.; Maguire, G.E.; Parboosing, R.; Sayed, Y.; Soliman, M.E.; Kruger, H.G. Synthesis, screening and computational investigation of pentacycloundecane-peptoids as potent CSA-HIV PR inhibitors. Eur. J. Med. Chem., 2012, 57, 459-467.
[http://dx.doi.org/10.1016/j.ejmech.2012.06.019] [PMID: 22867528]
[38]
Pawar, S.A.; Jabgunde, A.M.; Govender, P.; Maguire, G.E.; Kruger, H.G.; Parboosing, R.; Soliman, M.E.; Sayed, Y.; Dhavale, D.D.; Govender, T. Synthesis and molecular modelling studies of novel carbapeptide analogs for inhibition of HIV-1 protease. Eur. J. Med. Chem., 2012, 53, 13-21.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.027] [PMID: 22542107]
[39]
Makatini, M.M.; Petzold, K.; Alves, C.N.; Arvidsson, P.I.; Honarparvar, B.; Govender, P.; Govender, T.; Kruger, H.G.; Sayed, Y. JerônimoLameira; Maguire, G.E.; Soliman, M.E. Synthesis, 2D-NMR and molecular modelling studies of pentacycloundecane lactam-peptides and peptoids as potential HIV-1 wild type C-SA protease inhibitors. J. Enzyme Inhib. Med. Chem., 2013, 28(1), 78-88.
[http://dx.doi.org/10.3109/14756366.2011.633907] [PMID: 22339087]
[40]
Debouck, C. The HIV-1 protease as a therapeutic target for AIDS. AIDS Res. Hum. Retroviruses, 1992, 8(2), 153-164.
[http://dx.doi.org/10.1089/aid.1992.8.153] [PMID: 1540403]
[41]
King, N.M.; Prabu-Jeyabalan, M.; Nalivaika, E.A.; Schiffer, C.A. Combating susceptibility to drug resistance: lessons from HIV-1 protease. Chem. Biol., 2004, 11(10), 1333-1338.
[PMID: 15489160]
[42]
Prabu-Jeyabalan, M.; Nalivaika, E.A.; Romano, K.; Schiffer, C.A. Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate. J. Virol., 2006, 80(7), 3607-3616.
[http://dx.doi.org/10.1128/JVI.80.7.3607-3616.2006] [PMID: 16537628]
[43]
Ozer, N.; Haliloglu, T.; Schiffer, C.A. Substrate specificity in HIV-1 protease by a biased sequence search method. Proteins, 2006, 64(2), 444-456.
[http://dx.doi.org/10.1002/prot.21023] [PMID: 16741993]
[44]
Ozer, N.; Schiffer, C.A.; Haliloglu, T. Predicting substrate specificity in HIV-1 protease. In; Computer Aided Drug Design & Development Society in Turkey, 2006.
[45]
Cai, Y.; Yilmaz, N.K.; Myint, W.; Ishima, R.; Schiffer, C.A. Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation. J. Chem. Theory Comput., 2012, 8(10), 3452-3462.
[http://dx.doi.org/10.1021/ct300076y] [PMID: 23144597]
[46]
Shen, Y.; Altman, M.D.; Ali, A.; Nalam, M.N.; Cao, H.; Rana, T.M.; Schiffer, C.A.; Tidor, B. Testing the substrate-envelope hypothesis with designed pairs of compounds. ACS Chem. Biol., 2013, 8(11), 2433-2441.
[http://dx.doi.org/10.1021/cb400468c] [PMID: 23952265]
[47]
Perez, M.A.; Fernandes, P.A.; Ramos, M.J. Substrate recognition in HIV-1 protease: a computational study. J. Phys. Chem. B, 2010, 114(7), 2525-2532.
[http://dx.doi.org/10.1021/jp910958u] [PMID: 20121080]
[48]
Abdel-Rahman, H.M.; Al-karamany, G.S.; El-Koussi, N.A.; Youssef, A.F.; Kiso, Y. HIV protease inhibitors: peptidomimetic drugs and future perspectives. Curr. Med. Chem., 2002, 9(21), 1905-1922.
[http://dx.doi.org/10.2174/0929867023368890] [PMID: 12369875]
[49]
Tözsér, J.; Zahuczky, G.; Bagossi, P.; Louis, J.M.; Copeland, T.D.; Oroszlan, S.; Harrison, R.W.; Weber, I.T. Comparison of the substrate specificity of the human T-cell leukemia virus and human immunodeficiency virus proteinases. Eur. J. Biochem., 2000, 267(20), 6287-6295.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01714.x] [PMID: 11012683]
[50]
Jones, D.T.; Tress, M.; Bryson, K.; Hadley, C. Successful recognition of protein folds using threading methods biased by sequence similarity and predicted secondary structure. Proteins, 1999, 37(S3)(Suppl. 3), 104-111.
[http://dx.doi.org/10.1002/(SICI)1097-0134(1999)37:3+<104::AID-PROT14>3.0.CO;2-P] [PMID: 10526358]
[51]
Pitera, J.W.; Van Gunsteren, W.F. A comparison of non-bonded scaling approaches for free energy calculations. Mol. Simul., 2002, 28(1-2), 45-65.
[http://dx.doi.org/10.1080/08927020211973]
[52]
Shirts, M.R. Extremely precise free energy calculations of amino acid side chain analogs: Comparison of common molecular mechanics force fields for proteins. J. Chem. Phys., 2003, 119(11), 5740-5761.
[http://dx.doi.org/10.1063/1.1587119]
[53]
Blondel, A. Ensemble variance in free energy calculations by thermodynamic integration: theory, optimal “Alchemical” path, and practical solutions. J. Comput. Chem., 2004, 25(7), 985-993.
[http://dx.doi.org/10.1002/jcc.20025] [PMID: 15027110]
[54]
Özen, A.; Haliloğlu, T.; Schiffer, C.A. Dynamics of preferential substrate recognition in HIV-1 protease: redefining the substrate envelope. J. Mol. Biol., 2011, 410(4), 726-744.
[http://dx.doi.org/10.1016/j.jmb.2011.03.053] [PMID: 21762811]
[55]
Alder, B.J.; Wainwright, T.E. Studies in molecular dynamics. I. General method. J. Chem. Phys., 1959, 31(2), 459-466.
[http://dx.doi.org/10.1063/1.1730376]
[56]
Chellappan, S.; Kiran Kumar Reddy, G.S.; Ali, A.; Nalam, M.N.; Anjum, S.G.; Cao, H.; Kairys, V.; Fernandes, M.X.; Altman, M.D.; Tidor, B.; Rana, T.M.; Schiffer, C.A.; Gilson, M.K. Design of mutation-resistant HIV protease inhibitors with the substrate envelope hypothesis. Chem. Biol. Drug Des., 2007, 69(5), 298-313.
[http://dx.doi.org/10.1111/j.1747-0285.2007.00514.x] [PMID: 17539822]
[57]
Altman, M.D.; Ali, A.; Reddy, G.S.; Nalam, M.N.; Anjum, S.G.; Cao, H.; Chellappan, S.; Kairys, V.; Fernandes, M.X.; Gilson, M.K.; Schiffer, C.A.; Rana, T.M.; Tidor, B. HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants. J. Am. Chem. Soc., 2008, 130(19), 6099-6113.
[http://dx.doi.org/10.1021/ja076558p] [PMID: 18412349]
[58]
Nalam, M.N.; Schiffer, C.A. New approaches to HIV protease inhibitor drug design II: testing the substrate envelope hypothesis to avoid drug resistance and discover robust inhibitors. Curr. Opin. HIV AIDS, 2008, 3(6), 642-646.
[http://dx.doi.org/10.1097/COH.0b013e3283136cee] [PMID: 19373036]
[59]
Nalam, M.N.; Ali, A.; Altman, M.D.; Reddy, G.S.; Chellappan, S.; Kairys, V.; Ozen, A.; Cao, H.; Gilson, M.K.; Tidor, B.; Rana, T.M.; Schiffer, C.A. Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistance. J. Virol., 2010, 84(10), 5368-5378.
[http://dx.doi.org/10.1128/JVI.02531-09] [PMID: 20237088]
[60]
Alvizo, O.; Mittal, S.; Mayo, S.L.; Schiffer, C.A. Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease. Protein Sci., 2012, 21(7), 1029-1041.
[http://dx.doi.org/10.1002/pro.2086] [PMID: 22549928]
[61]
Dunbrack, R.L., Jr; Cohen, F.E. Bayesian statistical analysis of protein side-chain rotamer preferences. Protein Sci., 1997, 6(8), 1661-1681.
[http://dx.doi.org/10.1002/pro.5560060807] [PMID: 9260279]
[62]
Pettit, S.C.; Henderson, G.J.; Schiffer, C.A.; Swanstrom, R. Replacement of the P1 amino acid of human immunodeficiency virus type 1 Gag processing sites can inhibit or enhance the rate of cleavage by the viral protease. J. Virol., 2002, 76(20), 10226-10233.
[http://dx.doi.org/10.1128/JVI.76.20.10226-10233.2002] [PMID: 12239298]
[63]
Pettit, S.C.; Clemente, J.C.; Jeung, J.A.; Dunn, B.M.; Kaplan, A.H. Ordered processing of the human immunodeficiency virus type 1 GagPol precursor is influenced by the context of the embedded viral protease. J. Virol., 2005, 79(16), 10601-10607.
[http://dx.doi.org/10.1128/JVI.79.16.10601-10607.2005] [PMID: 16051852]
[64]
Beck, Z.Q.; Hervio, L.; Dawson, P.E.; Elder, J.H.; Madison, E.L. Identification of efficiently cleaved substrates for HIV-1 protease using a phage display library and use in inhibitor development. Virology, 2000, 274(2), 391-401.
[http://dx.doi.org/10.1006/viro.2000.0420] [PMID: 10964781]
[65]
Rhee, S-Y.; Taylor, J.; Fessel, W.J.; Kaufman, D.; Towner, W.; Troia, P.; Ruane, P.; Hellinger, J.; Shirvani, V.; Zolopa, A.; Shafer, R.W. HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob. Agents Chemother., 2010, 54(10), 4253-4261.
[http://dx.doi.org/10.1128/AAC.00574-10] [PMID: 20660676]
[66]
Nicholls, A.; Sharp, K.A.; Honig, B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins, 1991, 11(4), 281-296.
[http://dx.doi.org/10.1002/prot.340110407] [PMID: 1758883]
[67]
Tie, Y.; Boross, P.I.; Wang, Y.F.; Gaddis, L.; Liu, F.; Chen, X.; Tozser, J.; Harrison, R.W.; Weber, I.T. Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. FEBS J., 2005, 272(20), 5265-5277.
[http://dx.doi.org/10.1111/j.1742-4658.2005.04923.x] [PMID: 16218957]
[68]
Özen, A.; Haliloğlu, T.; Schiffer, C.A. HIV-1 protease and substrate coevolution validates the substrate envelope as the substrate recognition pattern. J. Chem. Theory Comput., 2012, 8(2)
[http://dx.doi.org/10.1021/ct200668a] [PMID: 24348205]
[69]
Patick, A.K.; Duran, M.; Cao, Y.; Shugarts, D.; Keller, M.R.; Mazabel, E.; Knowles, M.; Chapman, S.; Kuritzkes, D.R.; Markowitz, M. Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Antimicrob. Agents Chemother., 1998, 42(10), 2637-2644.
[http://dx.doi.org/10.1128/AAC.42.10.2637] [PMID: 9756769]
[70]
Pai, V.B.; Nahata, M.C. Nelfinavir mesylate: a protease inhibitor. Ann. Pharmacother., 1999, 33(3), 325-339.
[http://dx.doi.org/10.1345/aph.18089] [PMID: 10200859]
[71]
Özer, N.; Özen, A.; Schiffer, C.A.; Haliloğlu, T. Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution. Evol. Appl., 2015, 8(2), 185-198.
[http://dx.doi.org/10.1111/eva.12241] [PMID: 25685193]
[72]
Atilgan, A.R.; Durell, S.R.; Jernigan, R.L.; Demirel, M.C.; Keskin, O.; Bahar, I. Anisotropy of fluctuation dynamics of proteins with an elastic network model. Biophys. J., 2001, 80(1), 505-515.
[http://dx.doi.org/10.1016/S0006-3495(01)76033-X] [PMID: 11159421]
[73]
Laco, G.S. HIV-1 protease substrate-groove: Role in substrate recognition and inhibitor resistance. Biochimie, 2015, 118, 90-103.
[http://dx.doi.org/10.1016/j.biochi.2015.08.009] [PMID: 26300060]
[74]
Wang, Y.; Dewdney, T.G.; Liu, Z.; Reiter, S.J.; Brunzelle, J.S.; Kovari, I.A.; Kovari, L.C. Higher desolvation energy reduces molecular recognition in multi-drug resistant HIV-1 protease. Biology (Basel), 2012, 1(1), 81-93.
[http://dx.doi.org/10.3390/biology1010081] [PMID: 24832048]
[75]
Laco, G.S. Retroviral proteases: correlating substrate recognition with both selected and native inhibitor resistance. J. Mol. Biochem., 2017, 6(2)
[76]
Liu, Z.; Wang, Y.; Brunzelle, J.; Kovari, I.A.; Kovari, L.C. Nine crystal structures determine the substrate envelope of the MDR HIV-1 protease. Protein J., 2011, 30(3), 173-183.
[http://dx.doi.org/10.1007/s10930-011-9316-2] [PMID: 21394574]
[77]
Yedidi, R.S.; Proteasa, G.; Martinez, J.L.; Vickrey, J.F.; Martin, P.D.; Wawrzak, Z.; Liu, Z.; Kovari, I.A.; Kovari, L.C. Contribution of the 80s loop of HIV-1 protease to the multidrug-resistance mechanism: crystallographic study of MDR769 HIV-1 protease variants. Acta Crystallogr. D Biol. Crystallogr., 2011, 67(Pt 6), 524-532.
[http://dx.doi.org/10.1107/S0907444911011541] [PMID: 21636892]
[78]
Liu, Z.; Wang, Y.; Yedidi, R.S.; Dewdney, T.G.; Reiter, S.J.; Brunzelle, J.S.; Kovari, I.A.; Kovari, L.C. Conserved hydrogen bonds and water molecules in MDR HIV-1 protease substrate complexes. Biochem. Biophys. Res. Commun., 2013, 430(3), 1022-1027.
[http://dx.doi.org/10.1016/j.bbrc.2012.12.045] [PMID: 23261453]
[79]
Deshmukh, L. Binding kinetics and substrate selectivity in HIV-1 protease−Gag interactions probed at atomic resolution by chemical exchange NMR. Proceedings of the National Academy of Sciences, 2017.
[http://dx.doi.org/10.1073/pnas.1716098114]
[80]
Maschera, B.; Darby, G.; Palú, G.; Wright, L.L.; Tisdale, M.; Myers, R.; Blair, E.D.; Furfine, E.S. Human immunodeficiency virus. Mutations in the viral protease that confer resistance to saquinavir increase the dissociation rate constant of the protease-saquinavir complex. J. Biol. Chem., 1996, 271(52), 33231-33235.
[http://dx.doi.org/10.1074/jbc.271.52.33231] [PMID: 8969180]
[81]
Tözsér, J.; Bagossi, P.; Weber, I.T.; Copeland, T.D.; Oroszlan, S. Comparative studies on the substrate specificity of avian myeloblastosis virus proteinase and lentiviral proteinases. J. Biol. Chem., 1996, 271(12), 6781-6788.
[http://dx.doi.org/10.1074/jbc.271.12.6781] [PMID: 8636100]
[82]
Fehér, A.; Weber, I.T.; Bagossi, P.; Boross, P.; Mahalingam, B.; Louis, J.M.; Copeland, T.D.; Torshin, I.Y.; Harrison, R.W.; Tözsér, J. Effect of sequence polymorphism and drug resistance on two HIV-1 Gag processing sites. Eur. J. Biochem., 2002, 269(16), 4114-4120.
[http://dx.doi.org/10.1046/j.1432-1033.2002.03105.x] [PMID: 12180988]
[83]
Tözsér, J.; Gustchina, A.; Weber, I.T.; Blaha, I.; Wondrak, E.M.; Oroszlan, S. Studies on the role of the S4 substrate binding site of HIV proteinases. FEBS Lett., 1991, 279(2), 356-360.
[http://dx.doi.org/10.1016/0014-5793(91)80186-7] [PMID: 2001747]
[84]
Altman, M.D.; Nalivaika, E.A.; Prabu-Jeyabalan, M.; Schiffer, C.A.; Tidor, B. Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV-1 protease. Proteins, 2008, 70(3), 678-694.
[http://dx.doi.org/10.1002/prot.21514] [PMID: 17729291]
[85]
Tripathi, A.; Fornabaio, M.; Spyrakis, F.; Mozzarelli, A.; Cozzini, P.; Kellogg, G.E. Complexity in modeling and understanding protonation states: computational titration of HIV-1-protease-inhibitor complexes. Chem. Biodivers., 2007, 4(11), 2564-2577.
[http://dx.doi.org/10.1002/cbdv.200790210] [PMID: 18027371]
[86]
Weber, I.T.; Waltman, M.J.; Mustyakimov, M.; Blakeley, M.P.; Keen, D.A.; Ghosh, A.K.; Langan, P.; Kovalevsky, A.Y. Joint X-ray/neutron crystallographic study of HIV-1 protease with clinical inhibitor amprenavir: insights for drug design. J. Med. Chem., 2013, 56(13), 5631-5635.
[http://dx.doi.org/10.1021/jm400684f] [PMID: 23772563]
[87]
Gerlits, O.; Wymore, T.; Das, A.; Shen, C.H.; Parks, J.M.; Smith, J.C.; Weiss, K.L.; Keen, D.A.; Blakeley, M.P.; Louis, J.M.; Langan, P.; Weber, I.T.; Kovalevsky, A. Long-range electrostatics-induced two-proton transfer captured by neutron crystallography in an enzyme catalytic site. Angew. Chem. Int. Ed. Engl., 2016, 55(16), 4924-4927.
[http://dx.doi.org/10.1002/anie.201509989] [PMID: 26958828]
[88]
Yamazaki, T. 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(23), 10791-10792.
[http://dx.doi.org/10.1021/ja00102a057]
[89]
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(11), 946-950.
[http://dx.doi.org/10.1038/nsb1196-946] [PMID: 8901873]
[90]
Wang, Y.X.; Freedberg, D.I.; Yamazaki, T.; Wingfield, P.T.; Stahl, S.J.; Kaufman, J.D.; Kiso, Y.; Torchia, D.A. Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272. Biochemistry, 1996, 35(31), 9945-9950.
[http://dx.doi.org/10.1021/bi961268z] [PMID: 8756455]
[91]
Yu, N.; Hayik, S.A.; Wang, B.; Liao, N.; Reynolds, C.H.; Merz, K.M. Jr Assigning the protonation states of the key aspartates in β-Secretase using QM/MM X-ray structure refinement. J. Chem. Theory Comput., 2006, 2(4), 1057-1069.
[http://dx.doi.org/10.1021/ct0600060] [PMID: 19079786]
[92]
Makatini, M.M.; Petzold, K.; Sriharsha, S.N.; Ndlovu, N.; Soliman, M.E.; Honarparvar, B.; Parboosing, R.; Naidoo, A.; Arvidsson, P.I.; Sayed, Y.; Govender, P.; Maguire, G.E.; Kruger, H.G.; Govender, T. Synthesis and structural studies of pentacycloundecane-based HIV-1 PR inhibitors: a hybrid 2D NMR and docking/QM/MM/MD approach. Eur. J. Med. Chem., 2011, 46(9), 3976-3985.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.071] [PMID: 21741133]
[93]
Ribeiro, A.J.M. Enzymatic Flexibility and Reaction Rate: A QM/MM Study of HIV-1 Protease. ACS Catal., 2015, 5(9), 5617-5626.
[http://dx.doi.org/10.1021/acscatal.5b00759]
[94]
Okimoto, N. Molecular Dynamics Study of HIV-1 Protease− Substrate Complex: Roles of the Water Molecules at the Loop Structures of the Active Site. J. Am. Chem. Soc., 2000, 122(23), 5613-5622.
[http://dx.doi.org/10.1021/ja9929178]
[95]
Okimoto, N. Molecular dynamics simulations of a complex of HIV-1 protease and substrate: substrate-dependent efficiency of catalytic activity. J. Mol. Struct. THEOCHEM, 2001, 543(1), 53-63.
[http://dx.doi.org/10.1016/S0166-1280(00)00834-4]
[96]
Itoh, S.G.; Damjanovic, A.; Brooks, B.R. pH Replica-Exchange Method Based on Discrete Protonation States. Biophys. J., 2012, 102(3), 40a-40a.
[http://dx.doi.org/10.1016/j.bpj.2011.11.246]
[97]
Li, H.; Robertson, A.D.; Jensen, J.H. Very fast empirical prediction and rationalization of protein pKa values. Proteins, 2005, 61(4), 704-721.
[http://dx.doi.org/10.1002/prot.20660] [PMID: 16231289]
[98]
Dolinsky, T.J. PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucle-ic Acids Research, 2007, 35(suppl_2), W522-W525.
[99]
Gordon, J.C. Nucleic Acids Research 2005, 33(suppl_2), W368-W371.
[100]
McGee, T.D., Jr; Edwards, J.; Roitberg, A.E. pH-REMD simulations indicate that the catalytic aspartates of HIV-1 protease exist primarily in a monoprotonated state. J. Phys. Chem. B, 2014, 118(44), 12577-12585.
[http://dx.doi.org/10.1021/jp504011c] [PMID: 25340507]
[101]
Piana, S.; Carloni, P. Conformational flexibility of the catalytic Asp dyad in HIV-1 protease: An ab initio study on the free enzyme. Proteins, 2000, 39(1), 26-36.
[http://dx.doi.org/10.1002/(SICI)1097-0134(20000401)39:1<26:AID-PROT3>3.0.CO;2-N] [PMID: 10737924]
[102]
Dodson, G.; Wlodawer, A. Catalytic triads and their relatives. Trends Biochem. Sci., 1998, 23(9), 347-352.
[http://dx.doi.org/10.1016/S0968-0004(98)01254-7] [PMID: 9787641]
[103]
Makatini, M.M.; Petzold, K.; Sriharsha, S.N.; Soliman, M.E.; Honarparvar, B.; Arvidsson, P.I.; Sayed, Y.; Govender, P.; Maguire, G.E.; Kruger, H.G.; Govender, T. Pentacycloundecane-based inhibitors of wild-type C-South African HIV-protease. Bioorg. Med. Chem. Lett., 2011, 21(8), 2274-2277.
[http://dx.doi.org/10.1016/j.bmcl.2011.02.105] [PMID: 21429747]
[104]
Meek, T.D.; Dayton, B.D.; Metcalf, B.W.; Dreyer, G.B.; Strickler, J.E.; Gorniak, J.G.; Rosenberg, M.; Moore, M.L.; Magaard, V.W.; Debouck, C. Human immunodeficiency virus 1 protease expressed in Escherichia coli behaves as a dimeric aspartic protease. Proc. Natl. Acad. Sci. USA, 1989, 86(6), 1841-1845.
[http://dx.doi.org/10.1073/pnas.86.6.1841] [PMID: 2648384]
[105]
Harte, W.E., Jr; Beveridge, D.L. Prediction of the protonation state of the active site aspartyl residues in HIV-1 protease-inhibitor complexes via molecular dynamics simulation. J. Am. Chem. Soc., 1993, 115(10), 3883-3886.
[http://dx.doi.org/10.1021/ja00063a005]
[106]
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(36), 8730-8737.
[http://dx.doi.org/10.1021/ja003145e] [PMID: 11535077]
[107]
Piana, S.; Carloni, P.; Rothlisberger, U. Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutations. Protein Sci., 2002, 11(10), 2393-2402.
[http://dx.doi.org/10.1110/ps.0206702] [PMID: 12237461]
[108]
Piana, S.; Carloni, P.; Parrinello, M. Role of conformational fluctuations in the enzymatic reaction of HIV-1 protease. J. Mol. Biol., 2002, 319(2), 567-583.
[http://dx.doi.org/10.1016/S0022-2836(02)00301-7] [PMID: 12051929]
[109]
Northrop, D.B. Follow the protons: a low-barrier hydrogen bond unifies the mechanisms of the aspartic proteases. Accounts. Chem. Res., 2001, 34(10), 790-797.
[http://dx.doi.org/10.1021/ar000184m] [PMID: 11601963]
[110]
Becke, A.D. A new mixing of Hartree–Fock and local density‐functional theories. J. Chem. Phys., 1993, 98(2), 1372-1377.
[http://dx.doi.org/10.1063/1.464304]
[111]
Rassolov, V.A. 6‐31G* basis set for third‐row atoms. J. Comput. Chem., 2001, 22(9), 976-984.
[http://dx.doi.org/10.1002/jcc.1058]
[112]
Bjelic, S.; Aqvist, J. Catalysis and linear free energy relationships in aspartic proteases. Biochemistry, 2006, 45(25), 7709-7723.
[http://dx.doi.org/10.1021/bi060131y] [PMID: 16784222]
[113]
Chatfield, D.C.; Brooks, B.R. HIV-1 protease cleavage mechanism elucidated with molecular-dynamics simulation. J. Am. Chem. Soc., 1995, 117(20), 5561-5572.
[http://dx.doi.org/10.1021/ja00125a018]
[114]
Trylska, J.; Grochowski, P.; McCammon, J.A. The role of hydrogen bonding in the enzymatic reaction catalyzed by HIV-1 protease. Protein Sci., 2004, 13(2), 513-528.
[http://dx.doi.org/10.1110/ps.03372304] [PMID: 14739332]
[115]
Rodriguez, E.J.; Angeles, T.S.; Meek, T.D. Use of nitrogen-15 kinetic isotope effects to elucidate details of the chemical mechanism of human immunodeficiency virus 1 protease. Biochemistry, 1993, 32(46), 12380-12385.
[http://dx.doi.org/10.1021/bi00097a015] [PMID: 8241126]
[116]
Lee, H.; Darden, T.A.; Pedersen, L.G. An ab initio quantum mechanical model for the catalytic mechanism of HIV-1 protease. J. Am. Chem. Soc., 1996, 118(16), 3946-3950.
[http://dx.doi.org/10.1021/ja9513188]
[117]
Liu, H.; Müller-Plathe, F.; van Gunsteren, W.F. A combined quantum/classical molecular dynamics study of the catalytic mechanism of HIV protease. J. Mol. Biol., 1996, 261(3), 454-469.
[http://dx.doi.org/10.1006/jmbi.1996.0476] [PMID: 8780786]
[118]
Silva, A.M.; Cachau, R.E.; Sham, H.L.; Erickson, J.W. Inhibition and catalytic mechanism of HIV-1 aspartic protease. J. Mol. Biol., 1996, 255(2), 321-346.
[http://dx.doi.org/10.1006/jmbi.1996.0026] [PMID: 8551523]
[119]
Okimoto, N. Gag protein hydrolysis mechanism by HIV-1 protease - Investigation by semiempirical molecular orbital method. Nippon Kagaku Kaishi, 1997, (4), 260-266.
[http://dx.doi.org/10.1246/nikkashi.1997.260]
[120]
Okimoto, N. Hydrolysis mechanism of the phenylalanine-proline peptide bond specific to HIV-1 protease: Investigation by the ab initio molecular orbital method. J. Am. Chem. Soc., 1999, 121(32), 7349-7354.
[http://dx.doi.org/10.1021/ja9841106]
[121]
Trylska, J.; Bała, P.; Geller, M.; Grochowski, P. Molecular dynamics simulations of the first steps of the reaction catalyzed by HIV-1 protease. Biophys. J., 2002, 83(2), 794-807.
[http://dx.doi.org/10.1016/S0006-3495(02)75209-0] [PMID: 12124265]
[122]
Krzemińska, A.; Moliner, V.; Świderek, K. Dynamic and Electrostatic Effects on the Reaction Catalyzed by HIV-1 Protease. J. Am. Chem. Soc., 2016, 138(50), 16283-16298.
[http://dx.doi.org/10.1021/jacs.6b06856] [PMID: 27935692]
[123]
Grochowski, P. Density functional based parametrization of a valence bond method and its applications in quantum‐classical molecular dynamics simulations of enzymatic reactions. Int. J. Quantum Chem., 1996, 60(6), 1143-1164.
[http://dx.doi.org/10.1002/(SICI)1097-461X(1996)60:6<1143:AID-QUA4>3.0.CO;2-#]
[124]
Trylska, J.; Grochowski, P.; Geller, M. Parameterization of the approximate valence bond (AVB) method to describe potential energy surface in the reaction catalyzed by HIV-1 protease. Int. J. Quantum Chem., 2001, 82(2), 86-103.
[http://dx.doi.org/10.1002/1097-461X(2001)82:2<86:AID-QUA1024>3.0.CO;2-E]
[125]
Hohenberg, P.; Kohn, W. Inhomogeneous electron gas. Phys. Rev., 1964, 136(3B), B864.
[http://dx.doi.org/10.1103/PhysRev.136.B864]
[126]
Møller, C.; Plesset, M.S. Note on an approximation treatment for many-electron systems. Phys. Rev., 1934, 46(7), 618.
[http://dx.doi.org/10.1103/PhysRev.46.618]
[127]
Hyland, L.J.; Tomaszek, T.A., Jr; Roberts, G.D.; Carr, S.A.; Magaard, V.W.; Bryan, H.L.; Fakhoury, S.A.; Moore, M.L.; Minnich, M.D.; Culp, J.S. Human immunodeficiency virus-1 protease. 1. Initial velocity studies and kinetic characterization of reaction intermediates by 18O isotope exchange. Biochemistry, 1991, 30(34), 8441-8453.
[http://dx.doi.org/10.1021/bi00098a023] [PMID: 1883830]
[128]
Hyland, L.J.; Tomaszek, T.A., Jr; 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(34), 8454-8463.
[http://dx.doi.org/10.1021/bi00098a024] [PMID: 1883831]
[129]
Antonov, V.K.; Ginodman, L.M.; Kapitannikov, Y.V.; Barshevskaya, T.N.; Gurova, A.G.; Rumsh, L.D. Mechanism of pepsin catalysis: general base catalysis by the active-site carboxylate ion. FEBS Lett., 1978, 88(1), 87-90.
[http://dx.doi.org/10.1016/0014-5793(78)80613-9] [PMID: 346376]
[130]
Antonov, V.K.; Ginodman, L.M.; Rumsh, L.D.; Kapitannikov, Y.V.; Barshevskaya, T.N.; Yavashev, L.P.; Gurova, A.G.; Volkova, L.I. Studies on the mechanisms of action of proteolytic enzymes using heavy oxygen exchange. Eur. J. Biochem., 1981, 117(1), 195-200.
[http://dx.doi.org/10.1111/j.1432-1033.1981.tb06321.x] [PMID: 6790282]
[131]
Kumar, M.; Prashar, V.; Mahale, S.; Hosur, M.V. Observation of a tetrahedral reaction intermediate in the HIV-1 protease-substrate complex. Biochem. J., 2005, 389(Pt 2), 365-371.
[http://dx.doi.org/10.1042/BJ20041804] [PMID: 15794743]
[132]
Kipp, D.R.; Hirschi, J.S.; Wakata, A.; Goldstein, H.; Schramm, V.L. Transition states of native and drug-resistant HIV-1 protease are the same. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(17), 6543-6548.
[http://dx.doi.org/10.1073/pnas.1202808109] [PMID: 22493227]
[133]
Torrie, G.M.; Valleau, J.P. Monte Carlo free energy estimates using non-Boltzmann sampling: Application to the sub-critical Lennard-Jones fluid. Chem. Phys. Lett., 1974, 28(4), 578-581.
[http://dx.doi.org/10.1016/0009-2614(74)80109-0]
[134]
Kästner, J. Umbrella sampling. Wiley Interdiscip. Rev. Comput. Mol. Sci., 2011, 1(6), 932-942.
[http://dx.doi.org/10.1002/wcms.66]
[135]
Laio, A.; VandeVondele, J.; Rothlisberger, U. A Hamiltonian electrostatic coupling scheme for hybrid Car–Parrinello molecular dynamics simulations. J. Chem. Phys., 2002, 116(16), 6941-6947.
[http://dx.doi.org/10.1063/1.1462041]
[136]
Becke, A.D. Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A Gen. Phys., 1988, 38(6), 3098-3100.
[http://dx.doi.org/10.1103/PhysRevA.38.3098] [PMID: 9900728]
[137]
Lee, C.; Yang, W.; Parr, R.G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B Condens. Matter, 1988, 37(2), 785-789.
[http://dx.doi.org/10.1103/PhysRevB.37.785] [PMID: 9944570]
[138]
Kresse, G.; Furthmüller, J. Efficiency of ab-initio total energy calculations for metals and semiconductors using a plane-wave basis set. Comput. Mater. Sci., 1996, 6(1), 15-50.
[http://dx.doi.org/10.1016/0927-0256(96)00008-0]
[139]
Miller, M.; Schneider, J.; Sathyanarayana, B.K.; Toth, M.V.; Marshall, G.R.; Clawson, L.; Selk, L.; Kent, S.B.; Wlodawer, A. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution. Science, 1989, 246(4934), 1149-1152.
[http://dx.doi.org/10.1126/science.2686029] [PMID: 2686029]
[140]
Schock, H.B.; Garsky, V.M.; Kuo, L.C. Mutational anatomy of an HIV-1 protease variant conferring cross-resistance to protease inhibitors in clinical trials. Compensatory modulations of binding and activity. J. Biol. Chem., 1996, 271(50), 31957-31963.
[http://dx.doi.org/10.1074/jbc.271.50.31957] [PMID: 8943242]
[141]
Aqvist, J.; Warshel, A. Simulation of Enzyme-Reactions using Valence-Bond Force-Fields and other Hybrid Quantum-Classical Approaches. Chem. Rev., 1993, 93(7), 2523-2544.
[http://dx.doi.org/10.1021/cr00023a010]
[142]
Kamerlin, S.C.L.; Warshel, A. The empirical valence bond model: theory and applications. Wiley Interdiscip. Rev. Comput. Mol. Sci., 2011, 1(1), 30-45.
[http://dx.doi.org/10.1002/wcms.10]
[143]
Warshel, A. Computer modeling of chemical reactions in enzymes and solutions; Wiley New York, 1991.
[144]
Bitencourt-Ferreira, G.; de Azevedo, W.F. Development of a machine-learning model to predict Gibbs free energy of binding for protein-ligand complexes. Biophys. Chem., 2018, 240, 63-69.
[http://dx.doi.org/10.1016/j.bpc.2018.05.010] [PMID: 29906639]
[145]
Lima, A.N.; Philot, E.A.; Trossini, G.H.; Scott, L.P.; Maltarollo, V.G.; Honorio, K.M. Use of machine learning approaches for novel drug discovery. Expert Opin. Drug Discov., 2016, 11(3), 225-239.
[http://dx.doi.org/10.1517/17460441.2016.1146250] [PMID: 26814169]
[146]
Xavier, M.M.; Heck, G.S.; Avila, M.B.; Levin, N.M.B.; Pintro, V.O.; Carvalho, N.L.; Azevedo, W.F. SAnDReS a computational tool for statistical analysis of docking results and development of scoring functions. Comb. Chem. High Throughput Screen., 2016, 19(10), 801-812.
[http://dx.doi.org/10.2174/1386207319666160927111347] [PMID: 27686428]
[147]
Cascella, M.; Micheletti, C.; Rothlisberger, U.; Carloni, P. Evolutionarily conserved functional mechanics across pepsin-like and retroviral aspartic proteases. J. Am. Chem. Soc., 2005, 127(11), 3734-3742.
[http://dx.doi.org/10.1021/ja044608+] [PMID: 15771507]
[148]
Schramm, V.L. Transition States, analogues, and drug development. ACS Chem. Biol., 2013, 8(1), 71-81.
[http://dx.doi.org/10.1021/cb300631k] [PMID: 23259601]
[149]
Kipp, D.R.; Silva, R.G.; Schramm, V.L. Mass-dependent bond vibrational dynamics influence catalysis by HIV-1 protease. J. Am. Chem. Soc., 2011, 133(48), 19358-19361.
[http://dx.doi.org/10.1021/ja209391n] [PMID: 22059645]
[150]
Torbeev, V.Y.; Raghuraman, H.; Hamelberg, D.; Tonelli, M.; Westler, W.M.; Perozo, E.; Kent, S.B. Protein conformational dynamics in the mechanism of HIV-1 protease catalysis. Proc. Natl. Acad. Sci. USA, 2011, 108(52), 20982-20987.
[http://dx.doi.org/10.1073/pnas.1111202108] [PMID: 22158985]
[151]
Polgár, L.; Szeltner, Z.; Boros, I. Substrate-dependent mechanisms in the catalysis of human immunodeficiency virus protease. Biochemistry, 1994, 33(31), 9351-9357.
[http://dx.doi.org/10.1021/bi00197a040] [PMID: 8049236]
[152]
Becke, A.D. Density‐functional thermochemistry. I. The effect of the exchange‐only gradient correction. J. Chem. Phys., 1992, 96(3), 2155-2160.
[http://dx.doi.org/10.1063/1.462066]
[153]
Kovalevsky, A.Y.; Chumanevich, A.A.; Liu, F.; Louis, J.M.; Weber, I.T. Caught in the Act: the 1.5 A resolution crystal structures of the HIV-1 protease and the I54V mutant reveal a tetrahedral reaction intermediate. Biochemistry, 2007, 46(51), 14854-14864.
[http://dx.doi.org/10.1021/bi700822g] [PMID: 18052235]
[154]
Shen, C.H.; Tie, Y.; Yu, X.; Wang, Y.F.; Kovalevsky, A.Y.; Harrison, R.W.; Weber, I.T. Capturing the reaction pathway in near-atomic-resolution crystal structures of HIV-1 protease. Biochemistry, 2012, 51(39), 7726-7732.
[http://dx.doi.org/10.1021/bi3008092] [PMID: 22963370]
[155]
Darden, T.; Perera, L.; Li, L.; Pedersen, L. New tricks for modelers from the crystallography toolkit: the particle mesh Ewald algorithm and its use in nucleic acid simulations. Structure, 1999, 7(3), R55-R60.
[http://dx.doi.org/10.1016/S0969-2126(99)80033-1] [PMID: 10368306]
[156]
Godbout, N. Optimization of Gaussian-type basis sets for local spin density functional calculations. Part I. Boron through neon, optimization technique and validation. Can. J. Chem., 1992, 70(2), 560-571.
[http://dx.doi.org/10.1139/v92-079]
[157]
Binkley, J.S.; Pople, J.A.; Hehre, W.J. Self-consistent molecular orbital methods. 21. Small split-valence basis sets for first-row elements. J. Am. Chem. Soc., 1980, 102(3), 939-947.
[http://dx.doi.org/10.1021/ja00523a008]
[158]
Gordon, M.S. Self-consistent molecular-orbital methods. 22. Small split-valence basis sets for second-row elements. J. Am. Chem. Soc., 1982, 104(10), 2797-2803.
[http://dx.doi.org/10.1021/ja00374a017]
[159]
Hehre, W.J.; Stewart, R.F.; Pople, J.A. self‐consistent molecular‐orbital methods. i. use of gaussian expansions of Slater‐type atomic orbitals. J. Chem. Phys., 1969, 51(6), 2657-2664.
[http://dx.doi.org/10.1063/1.1672392]
[160]
Collins, J.B. Self‐consistent molecular orbital methods. XVII. Geometries and binding energies of second‐row molecules. A comparison of three basis sets. J. Chem. Phys., 1976, 64(12), 5142-5151.
[http://dx.doi.org/10.1063/1.432189]
[161]
Duan, Y.; Wu, C.; Chowdhury, S.; Lee, M.C.; Xiong, G.; Zhang, W.; Yang, R.; Cieplak, P.; Luo, R.; Lee, T.; Caldwell, J.; Wang, J.; Kollman, P. A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J. Comput. Chem., 2003, 24(16), 1999-2012.
[http://dx.doi.org/10.1002/jcc.10349] [PMID: 14531054]
[162]
Gerritzen, D. Limba, and H.-H., NMR Spectroscopy. J. Am. Chem. Soc., 1984, 106(4), 869-879.
[http://dx.doi.org/10.1021/ja00316a007]
[163]
Cleland, W.W. Low-barrier hydrogen bonds and enzymatic catalysis. Arch. Biochem. Biophys., 2000, 382(1), 1-5.
[http://dx.doi.org/10.1006/abbi.2000.2011] [PMID: 11051090]
[164]
Kruger, H.G. Ab initio mechanistic study of the protection of alcohols and amines with anhydrides. J. Mol. Struct. THEOCHEM, 2002, 577(2), 281-285.
[http://dx.doi.org/10.1016/S0166-1280(01)00672-8]
[165]
Gokul, V. An ab initio mechanistic understanding of the regioselective acetylation of 8,11-dihydroxy-pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)] undecane-8,11-lactam. J. Mol. Struct. THEOCHEM, 2004, 672(1-3), 119-125.
[http://dx.doi.org/10.1016/j.theochem.2003.11.011]
[166]
Kruger, H.G. Experimental and computational studies of the regioselective protection of hydantoins using anhydride. J. Mol. Struct. THEOCHEM, 2006, 771(1-3), 165-170.
[http://dx.doi.org/10.1016/j.theochem.2006.03.037]
[167]
Singh, T. Theoretical study on the formation of a pentacyclo-undecane cage lactam. Comput. Theor. Chem., 2012, 986, 63-70.
[http://dx.doi.org/10.1016/j.comptc.2012.02.011]
[168]
Md Abdur Rauf, S.; Arvidsson, P.I.; Albericio, F.; Govender, T.; Maguire, G.E.; Kruger, H.G.; Honarparvar, B. The effect of N-methylation of amino acids (Ac-X-OMe) on solubility and conformation: a DFT study. Org. Biomol. Chem., 2015, 13(39), 9993-10006.
[http://dx.doi.org/10.1039/C5OB01565K] [PMID: 26289381]
[169]
Lawal, M.M.; Govender, T.; Maguire, G.E.; Honarparvar, B.; Kruger, H.G. Mechanistic investigation of the uncatalyzed esterification reaction of acetic acid and acid halides with methanol: a DFT study. J. Mol. Model., 2016, 22(10), 235.
[http://dx.doi.org/10.1007/s00894-016-3084-z] [PMID: 27604278]
[170]
Fakhar, Z. Computational model for the acylation step of the β-lactam ring: Potential application for l, d-transpeptidase 2 in mycobacterium tuberculosis. J. Mol. Struct., 2017, 1128, 94-102.
[http://dx.doi.org/10.1016/j.molstruc.2016.08.049]
[171]
Rose, R.B.; Craik, C.S.; Douglas, N.L.; Stroud, R.M. Three-dimensional structures of HIV-1 and SIV protease product complexes. Biochemistry, 1996, 35(39), 12933-12944.
[http://dx.doi.org/10.1021/bi9612733] [PMID: 8841139]
[172]
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(49), 18464-18469.
[http://dx.doi.org/10.1073/pnas.0605809103] [PMID: 17116869]
[173]
Brünger, A.T.; Adams, P.D.; Clore, G.M.; DeLano, W.L.; Gros, P.; Grosse-Kunstleve, R.W.; Jiang, J.S.; Kuszewski, J.; Nilges, M.; Pannu, N.S.; Read, R.J.; Rice, L.M.; Simonson, T.; Warren, G.L. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D Biol. Crystallogr., 1998, 54(Pt 5), 905-921.
[http://dx.doi.org/10.1107/S0907444998003254] [PMID: 9757107]
[174]
Bihani, S.; Das, A.; Prashar, V.; Ferrer, J.L.; Hosur, M.V. X-ray structure of HIV-1 protease in situ product complex. Proteins, 2009, 74(3), 594-602.
[http://dx.doi.org/10.1002/prot.22174] [PMID: 18704947]
[175]
Kumar, M.; Kannan, K.K.; Hosur, M.V.; Bhavesh, N.S.; Chatterjee, A.; Mittal, R.; Hosur, R.V. Effects of remote mutation on the autolysis of HIV-1 PR: X-ray and NMR investigations. Biochem. Biophys. Res. Commun., 2002, 294(2), 395-401.
[http://dx.doi.org/10.1016/S0006-291X(02)00482-5] [PMID: 12051725]
[176]
Prashar, V.; Bihani, S.; Das, A.; Ferrer, J.L.; Hosur, M. Catalytic water co-existing with a product peptide in the active site of HIV-1 protease revealed by X-ray structure analysis. PLoS One, 2009, 4(11), e7860
[http://dx.doi.org/10.1371/journal.pone.0007860] [PMID: 19924250]
[177]
Das, A.; Mahale, S.; Prashar, V.; Bihani, S.; Ferrer, J.L.; Hosur, M.V. X-ray snapshot of HIV-1 protease in action: observation of tetrahedral intermediate and short ionic hydrogen bond SIHB with catalytic aspartate. J. Am. Chem. Soc., 2010, 132(18), 6366-6373.
[http://dx.doi.org/10.1021/ja100002b] [PMID: 20397633]
[178]
Ichikawa, M. The C–O vs O–H length correlation in hydrogen-bonded carboxyl groups. Acta Crystallogr. B, 1979, 35(5), 1300-1301.
[http://dx.doi.org/10.1107/S0567740879006282]
[179]
Mittal, S.; Cai, Y.F.; Nalam, M.N.L.; Bolon, D.N.A.; Schiffer, C.A. Hydrophobic Core Flexibility Modulates Enzyme Activity in HIV-1 Protease. In: J. Am. Chem. Soc; Christov, C.; KarabenchevaChristova, T., Eds.. , 2012; 134, pp. (9)4163-4168.
[180]
Weber, I.T. Reaction Intermediates Discovered in Crystal Structures of Enzymes, in Structural and Mechanistic Enzymology In: Bringing Together Experiments and Computing; Christov, C.; KarabenchevaChristova, T., Eds.. 57.
[http://dx.doi.org/10.1021/ja2095766]
[181]
Calixto, A.R.; Ramos, M.J.; Fernandes, P.A. Influence of frozen residues on the exploration of the PES of enzyme reaction mechanisms. J. Chem. Theory Comput., 2017, 13(11), 5486-5495.
[http://dx.doi.org/10.1021/acs.jctc.7b00768] [PMID: 28992703]
[182]
Mahalingam, A.K.; Axelsson, L.; Ekegren, J.K.; Wannberg, J.; Kihlström, J.; Unge, T.; Wallberg, H.; Samuelsson, B.; Larhed, M.; Hallberg, A. HIV-1 protease inhibitors with a transition-state mimic comprising a tertiary alcohol: improved antiviral activity in cells. J. Med. Chem., 2010, 53(2), 607-615.
[http://dx.doi.org/10.1021/jm901165g] [PMID: 19961222]
[183]
Carnevale, V. On the nature of the reaction intermediate in the HIV-1 protease: a quantum chemical study. Comput. Phys. Commun., 2008, 179(1-3), 120-123.
[http://dx.doi.org/10.1016/j.cpc.2008.01.032]
[184]
Svensson, M. ONIOM: a multilayered integrated MO+ MM method for geometry optimizations and single point energy predictions. A test for Diels− Alder reactions and Pt (P (t-Bu) 3) 2+ H2 oxidative addition. J. Phys. Chem., 1996, 100(50), 19357-19363.
[http://dx.doi.org/10.1021/jp962071j]
[185]
Chung, L.W.; Sameera, W.M.; Ramozzi, R.; Page, A.J.; Hatanaka, M.; Petrova, G.P.; Harris, T.V.; Li, X.; Ke, Z.; Liu, F.; Li, H.B.; Ding, L.; Morokuma, K. The ONIOM method and its applications. Chem. Rev., 2015, 115(12), 5678-5796.
[http://dx.doi.org/10.1021/cr5004419] [PMID: 25853797]
[186]
Jaskólski, M.; Tomasselli, A.G.; Sawyer, T.K.; Staples, D.G.; Heinrikson, R.L.; Schneider, J.; Kent, S.B.; Wlodawer, A. Structure at 2.5-A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylene-based inhibitor. Biochemistry, 1991, 30(6), 1600-1609.
[http://dx.doi.org/10.1021/bi00220a023] [PMID: 1993177]
[187]
Lawal, M.M. DFT study of the acid‐catalyzed esterification reaction mechanism of methanol with carboxylic acid and its halide derivatives. Int. J. Quantum Chem., 2017.
[188]
Wang, Y-X. Bound water molecules at the interface between the HIV-1 protease and a potent inhibitor, KNI-272, determined by NMR. J. Am. Chem. Soc., 1996, 118(49), 12287-12290.
[http://dx.doi.org/10.1021/ja962612i]
[189]
Li, Z.; Lazaridis, T. Thermodynamic contributions of the ordered water molecule in HIV-1 protease. J. Am. Chem. Soc., 2003, 125(22), 6636-6637.
[http://dx.doi.org/10.1021/ja0299203] [PMID: 12769565]
[190]
Ghosh, A.K.; Gemma, S.; Baldridge, A.; Wang, Y.F.; Kovalevsky, A.Y.; Koh, Y.; Weber, I.T.; Mitsuya, H. Flexible cyclic ethers/polyethers as novel P2-ligands for HIV-1 protease inhibitors: design, synthesis, biological evaluation, and protein-ligand X-ray studies. J. Med. Chem., 2008, 51(19), 6021-6033.
[http://dx.doi.org/10.1021/jm8004543] [PMID: 18783203]
[191]
Shen, C.H.; Wang, Y.F.; Kovalevsky, A.Y.; Harrison, R.W.; Weber, I.T. Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters. FEBS J., 2010, 277(18), 3699-3714.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07771.x] [PMID: 20695887]

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