D. Tebit and E. Arts, Tracking a century of global expansion and evolution of HIV to drive understanding and to combat disease, The Lancet Infectious Diseases, vol.11, issue.1, pp.45-56, 2011.
DOI : 10.1016/S1473-3099(10)70186-9

R. Lessells, D. Katzenstein, and T. De-oliveira, Are subtype differences important in HIV drug resistance? Current opinion in virology, pp.636-643, 2012.

X. Qiu and Z. Liu, Recent developments of peptidomimetic HIV-1 protease inhibitors. Current medicinal chemistry, pp.4513-4537, 2011.

A. Perryman, J. Lin, and J. Mccammon, HIV-1 protease molecular dynamics of a wild-type and of the V82F/I84V mutant: Possible contributions to drug resistance and a potential new target site for drugs, Protein Science, vol.315, issue.4, pp.1108-1123, 2004.
DOI : 10.1110/ps.03468904

P. Batista, G. Pandey, P. Pascutti, P. Bisch, D. Perahia et al., Free Energy Profiles along Consensus Normal Modes Provide Insight into HIV-1 Protease Flap Opening, Journal of Chemical Theory and Computation, vol.7, issue.8, pp.2348-2352, 2011.
DOI : 10.1021/ct200237u

P. Batista, C. Robert, J. Marechal, B. Hamida-rebai, M. Pascutti et al., Consensus modes, a robust description of protein collective motions from multiple-minima normal mode analysisapplication to the HIV-1 protease, Phys Chem Chem Phys, issue.12, pp.122850-2859, 2010.

M. Prabu-jeyabalan, E. Nalivaika, and C. Schiffer, How does a symmetric dimer recognize an asymmetric substrate? a substrate complex of HIV-1 protease, Journal of Molecular Biology, vol.301, issue.5, pp.1207-1220, 2000.
DOI : 10.1006/jmbi.2000.4018

M. Prabu-jeyabalan, E. Nalivaika, and C. Schiffer, Substrate Shape Determines Specificity of Recognition for HIV-1 Protease, Structure, vol.10, issue.3, pp.369-381, 2002.
DOI : 10.1016/S0969-2126(02)00720-7

J. Nkengasong, C. Adje-toure, and P. Weidle, HIV antiretroviral drug resistance in Africa, AIDS reviews, vol.6, issue.1, pp.4-12, 2004.

A. Holguin, A. Alvarez, and V. Soriano, High prevalence of HIV-1 subtype G and natural polymorphisms at the protease gene among HIV-infected immigrants in Madrid, AIDS, vol.16, issue.8, pp.1163-1170, 2002.
DOI : 10.1097/00002030-200205240-00010

A. Papa, E. Papadimitriou, and A. Papoutsi, Antoniadis A: M36I, protease gene, HIV-1: resistant mutation or genetic polymorphism? Aids, pp.1858-1859, 2003.

V. Johnson, V. Calvez, H. Gunthard, R. Paredes, D. Pillay et al., update of the drug resistance mutations in HIV-1. Topics in antiviral medicine, pp.2011156-164, 2011.

P. Batista, A. Wilter, E. Durham, and P. Pascutti, Molecular dynamics simulations applied to the study of subtypes of HIV-1 protease common to Brazil, Africa, and Asia. Cell biochemistry and biophysics, pp.395-404, 2006.

H. Ode, S. Matsuyama, M. Hata, S. Neya, J. Kakizawa et al., Computational Characterization of Structural Role of the Non-active Site Mutation M36I of Human Immunodeficiency Virus Type 1 Protease, Journal of Molecular Biology, vol.370, issue.3, pp.598-607, 2007.
DOI : 10.1016/j.jmb.2007.04.081

O. Alvizo, S. Mittal, S. Mayo, and C. Schiffer, Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease, Protein Science, vol.60, issue.7, pp.1029-1041
DOI : 10.1002/pro.2086

R. Soares, P. Batista, M. Costa, L. Dardenne, P. Pascutti et al., Understanding the HIV-1 protease nelfinavir resistance mutation D30N in subtypes B and C through molecular dynamics simulations, Journal of Molecular Graphics and Modelling, vol.29, issue.2, pp.137-147, 2010.
DOI : 10.1016/j.jmgm.2010.05.007

P. Batista, M. Costa, P. Pascutti, P. Bisch, and W. De-souza, High temperatures enhance cooperative motions between CBM and catalytic domains of a thermostable cellulase: mechanism insights from essential dynamics, Physical Chemistry Chemical Physics, vol.28, issue.116, pp.1313709-13720, 2011.
DOI : 10.1039/c0cp02697b

F. Ding, M. Layten, and C. Simmerling, Solution Structure of HIV-1 Protease Flaps Probed by Comparison of Molecular Dynamics Simulation Ensembles and EPR Experiments, Journal of the American Chemical Society, vol.130, issue.23, pp.7184-7185, 2008.
DOI : 10.1021/ja800893d

M. Sanches, S. Krauchenco, N. Martins, A. Gustchina, A. Wlodawer et al., Structural Characterization of B and non-B Subtypes of HIV-Protease: Insights into the Natural Susceptibility to Drug Resistance Development, Journal of Molecular Biology, vol.369, issue.4, pp.1029-1040, 2007.
DOI : 10.1016/j.jmb.2007.03.049

H. Ode, M. Yokoyama, T. Kanda, and H. Sato, Identification of folding preferences of cleavage junctions of HIV-1 precursor proteins for regulation of cleavability, Journal of Molecular Modeling, vol.122, issue.2, pp.391-399, 2011.
DOI : 10.1007/s00894-010-0739-z

M. Costa, P. Batista, C. Shida, C. Robert, P. Bisch et al., How does heparin prevent the pH inactivation of cathepsin B? Allosteric mechanism elucidated by docking and molecular dynamics, BMC Genomics, vol.11, issue.Suppl 5, pp.11-16, 2010.
DOI : 10.1063/1.470117

S. Hayward and B. De-groot, Normal Modes and Essential Dynamics, Molecular Modeling of Proteins, p.443, 2008.
DOI : 10.1007/978-1-59745-177-2_5
URL : http://hdl.handle.net/11858/00-001M-0000-0012-DD7B-8

A. Amadei, M. Ceruso, D. Nola, and A. , On the convergence of the conformational coordinates basis set obtained by the essential dynamics analysis of proteins' molecular dynamics simulations, Proteins: Structure, Function, and Genetics, vol.35, issue.4, pp.419-424, 1999.
DOI : 10.1002/(SICI)1097-0134(19990901)36:4<419::AID-PROT5>3.0.CO;2-U

B. Hess, Convergence of sampling in protein simulations. Physical review, p.31910, 2002.

B. Horta, J. Cirino, and R. De-alencastro, On the structure, interactions, and dynamics of bound VEGF, Journal of Molecular Graphics and Modelling, vol.26, issue.7, pp.1091-1103, 2008.
DOI : 10.1016/j.jmgm.2007.10.001

T. Hou, W. Mclaughlin, and W. Wang, Evaluating the potency of HIV-1 protease drugs to combat resistance, Proteins: Structure, Function, and Bioinformatics, vol.330, issue.3, pp.1163-1174, 2008.
DOI : 10.1002/prot.21808

D. Ferguson, R. Radmer, and P. Kollman, Determination of the relative binding free energies of peptide inhibitors to the HIV-1 protease, Journal of Medicinal Chemistry, vol.34, issue.8, pp.2654-2659, 1991.
DOI : 10.1021/jm00112a048

T. Hou and R. Yu, Molecular dynamics and free energy studies on the wildtype and double mutant HIV-1 protease complexed with amprenavir and two amprenavir-related inhibitors: mechanism for binding and drug resistance, Journal of medicinal chemistry, issue.6, pp.501177-1188, 2007.

I. Stoica, S. Sadiq, and P. Coveney, Rapid and Accurate Prediction of Binding Free Energies for Saquinavir-Bound HIV-1 Proteases, Journal of the American Chemical Society, vol.130, issue.8, pp.2639-2648, 2008.
DOI : 10.1021/ja0779250

A. Velazquez-campoy, M. Todd, S. Vega, and E. Freire, Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes, Proceedings of the National Academy of Sciences, vol.98, issue.11, pp.986062-6067, 2001.
DOI : 10.1073/pnas.111152698

A. Ozen, T. Haliloglu, and C. Schiffer, HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern, J Chem Theory Comput, vol.2012, issue.82, pp.703-714

B. Hess, C. Kutzner, D. Van-der-spoel, and E. Lindahl, GROMACS 4:?? Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation, Journal of Chemical Theory and Computation, vol.4, issue.3, p.435, 2008.
DOI : 10.1021/ct700301q

V. Hornak, R. Abel, A. Okur, B. Strockbine, A. Roitberg et al., Comparison of multiple Amber force fields and development of improved protein backbone parameters, Proteins: Structure, Function, and Bioinformatics, vol.43, issue.3, pp.712-725, 2006.
DOI : 10.1002/prot.21123

W. Jorgensen, J. Chandrasekhar, J. Madura, R. Impey, and M. Klein, Comparison of simple potential functions for simulating liquid water, The Journal of Chemical Physics, vol.79, issue.2, pp.926-935, 1983.
DOI : 10.1063/1.445869

B. Hess, H. Bekker, H. Berendsen, and J. Fraaije, LINCS: A linear constraint solver for molecular simulations, Journal of Computational Chemistry, vol.19, issue.12, pp.1463-1472, 1997.
DOI : 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H

S. Miyamoto and P. Kollman, Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models, Journal of Computational Chemistry, vol.114, issue.8, pp.952-962, 1992.
DOI : 10.1002/jcc.540130805

G. Bussi, D. Donadio, and M. Parrinello, Canonical sampling through velocity rescaling. The Journal of chemical physics, p.14101, 2007.
DOI : 10.1063/1.2408420
URL : http://arxiv.org/abs/0803.4060

H. Berendsen, J. Postma, W. Vangunsteren, A. Dinola, and J. Haak, Molecular dynamics with coupling to an external bath, The Journal of Chemical Physics, vol.81, issue.8, pp.3684-3690, 1984.
DOI : 10.1063/1.448118

E. Ulrich, P. Lalith, L. Max, D. Tom, L. Hsing et al., A smooth particle mesh Ewald method, J Chem Phys, vol.103, pp.8577-8593, 1995.

B. Lee and F. Richards, The interpretation of protein structures: Estimation of static accessibility, Journal of Molecular Biology, vol.55, issue.3, pp.379-400, 1971.
DOI : 10.1016/0022-2836(71)90324-X

P. Valiente, P. Batista, A. Pupo, T. Pons, A. Valencia et al., Predicting functional residues in Plasmodium falciparum plasmepsins by combining sequence and structural analysis with molecular dynamics simulations, Proteins: Structure, Function, and Bioinformatics, vol.280, issue.2, pp.440-457, 2008.
DOI : 10.1002/prot.22068

M. Connolly, Solvent-accessible surfaces of proteins and nucleic acids, Science, vol.221, issue.4612, pp.709-713, 1983.
DOI : 10.1126/science.6879170

P. Kollman, I. Massova, C. Reyes, B. Kuhn, S. Huo et al., Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models, Accounts of chemical research, issue.12, pp.33889-897, 2000.

I. Massova and P. Kollman, Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding. Perspectives in Drug Discovery and Design, pp.113-135, 2000.

B. Kuhn, P. Gerber, T. Schulz-gasch, and M. Stahl, Validation and Use of the MM-PBSA Approach for Drug Discovery, Journal of Medicinal Chemistry, vol.48, issue.12, pp.484040-4048, 2005.
DOI : 10.1021/jm049081q

J. Wang, T. Hou, and X. Xu, Recent Advances in Free Energy Calculations with a Combination of Molecular Mechanics and Continuum Models, Current Computer Aided-Drug Design, vol.2, issue.3, pp.287-306, 2006.
DOI : 10.2174/157340906778226454

T. Hou, J. Wang, Y. Li, and W. Wang, Assessing the Performance of the MM/PBSA and MM/GBSA Methods. 1. The Accuracy of Binding Free Energy Calculations Based on Molecular Dynamics Simulations, Journal of Chemical Information and Modeling, vol.51, issue.1, pp.69-82, 2011.
DOI : 10.1021/ci100275a

N. Baker, D. Sept, S. Joseph, M. Holst, and J. Mccammon, Electrostatics of nanosystems: Application to microtubules and the ribosome, Proceedings of the National Academy of Sciences, vol.98, issue.18, pp.9810037-10041, 2001.
DOI : 10.1073/pnas.181342398

M. Sanner, A. Olson, and J. Spehner, Reduced surface: An efficient way to compute molecular surfaces, Biopolymers, vol.9, issue.3, pp.305-320, 1996.
DOI : 10.1002/(SICI)1097-0282(199603)38:3<305::AID-BIP4>3.0.CO;2-Y

B. Hess, Similarities between principal components of protein dynamics and random diffusion, Physical Review E, vol.62, issue.6, pp.8438-8448, 2000.
DOI : 10.1103/PhysRevE.62.8438