M. Stumpf, T. Thorne, E. De-silva, R. Stewart, H. An et al., Estimating the size of the human interactome, Proceedings of the National Academy of Sciences, vol.105, issue.19, pp.6959-6964, 2008.
DOI : 10.1073/pnas.0708078105

A. Cochran, Protein???protein interfaces: mimics and inhibitors, Current Opinion in Chemical Biology, vol.5, issue.6, pp.654-659, 2001.
DOI : 10.1016/S1367-5931(01)00262-9

J. Wells and C. Mcclendon, Reaching for high-hanging fruit in drug discovery at protein???protein interfaces, Nature, vol.12, issue.7172, pp.1001-1009, 2007.
DOI : 10.1038/nature06526

B. Villoutreix, K. Bastard, O. Sperandio, R. Fahraeus, J. Poyet et al., In Silico-In Vitro Screening of Protein-Protein Interactions: Towards the Next Generation of Therapeutics, Current Pharmaceutical Biotechnology, vol.9, issue.2, pp.103-122, 2008.
DOI : 10.2174/138920108783955218

URL : https://hal.archives-ouvertes.fr/inserm-00273685

R. Bourgeas, M. Basse, X. Morelli, and P. Roche, Atomic Analysis of Protein-Protein Interfaces with Known Inhibitors: The 2P2I Database, PLoS ONE, vol.5, issue.3, p.9598, 2010.
DOI : 10.1371/journal.pone.0009598.s006

J. Fuller, N. Burgoyne, and R. Jackson, Predicting druggable binding sites at the protein???protein interface, Drug Discovery Today, vol.14, issue.3-4, pp.155-161, 2009.
DOI : 10.1016/j.drudis.2008.10.009

C. Reynes, H. Host, A. Camproux, G. Laconde, F. Leroux et al., Designing Focused Chemical Libraries Enriched in Protein-Protein Interaction Inhibitors using Machine-Learning Methods, PLoS Computational Biology, vol.7, issue.3, p.1000695, 2010.
DOI : 10.1371/journal.pcbi.1000695.s004

URL : https://hal.archives-ouvertes.fr/inserm-00705646

O. Sperandio, C. Reynes, A. Camproux, and B. Villoutreix, Rationalizing the chemical space of protein???protein interaction inhibitors, Drug Discovery Today, vol.15, issue.5-6, pp.220-229, 2010.
DOI : 10.1016/j.drudis.2009.11.007

O. Kutzki, H. Park, J. Ernst, B. Orner, H. Yin et al., Antagonist Based on ??-Helix Mimicry, Journal of the American Chemical Society, vol.124, issue.40, pp.11838-11839, 2002.
DOI : 10.1021/ja026861k

H. Yin, G. Lee, K. Sedey, O. Kutzki, H. Park et al., Terphenyl-Based Bak BH3 alpha-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL, pp.10191-10196, 2005.

B. Orner, J. Ernst, and A. Hamilton, Toward Proteomimetics:?? Terphenyl Derivatives as Structural and Functional Mimics of Extended Regions of an ??-Helix, Journal of the American Chemical Society, vol.123, issue.22, pp.5382-5383, 2001.
DOI : 10.1021/ja0025548

K. Yap, J. Kim, K. Truong, M. Sherman, T. Yuan et al., Calmodulin Target Database, Journal of Structural and Functional Genomics, vol.1, issue.1, pp.8-14, 2000.
DOI : 10.1023/A:1011320027914

D. Chin and A. Means, Calmodulin: a prototypical calcium sensor, Trends in Cell Biology, vol.10, issue.8, pp.322-328, 2000.
DOI : 10.1016/S0962-8924(00)01800-6

J. Suever, Y. Chen, J. Mcdonald, and Y. Song, Conformation and Free Energy Analyses of the Complex of Calcium-Bound Calmodulin and the Fas Death Domain, Biophysical Journal, vol.95, issue.12, pp.5913-5921, 2008.
DOI : 10.1529/biophysj.108.130542

W. Meador, A. Means, and F. Quiocho, Target enzyme recognition by calmodulin: 2.4 A structure of a calmodulin-peptide complex, Science, vol.257, issue.5074, pp.1251-1255, 1992.
DOI : 10.1126/science.1519061

C. Drum, S. Yan, J. Bard, Y. Shen, D. Lu et al., Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin, Nature, vol.415, issue.6870, pp.396-402, 2002.
DOI : 10.1038/415396a

S. Bhattacharya, C. Bunick, and W. Chazin, Target selectivity in EF-hand calcium binding proteins, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, vol.1742, issue.1-3, pp.69-79, 2004.
DOI : 10.1016/j.bbamcr.2004.09.002

M. Figueroa, G. Mdel, C. Rodriguez-sotres, R. Sosa-peinado, A. Gonzalez-andrade et al., Calmodulin inhibitors from the fungus Emericella sp., Bioorganic & Medicinal Chemistry, vol.17, issue.6, pp.2167-2174, 2009.
DOI : 10.1016/j.bmc.2008.10.079

J. Salisbury, K. Suino, R. Busby, and S. M. , Centrin-2 Is Required for Centriole Duplication in Mammalian Cells, Current Biology, vol.12, issue.15, pp.1287-1292, 2002.
DOI : 10.1016/S0960-9822(02)01019-9

K. Resendes, B. Rasala, and D. Forbes, Centrin 2 Localizes to the Vertebrate Nuclear Pore and Plays a Role in mRNA and Protein Export, Molecular and Cellular Biology, vol.28, issue.5, pp.1755-1769, 2008.
DOI : 10.1128/MCB.01697-07

J. Saldivar, X. Wu, M. Follen, and D. Gershenson, Nucleotide excision repair pathway review I: Implications in ovarian cancer and platinum sensitivity, Gynecologic Oncology, vol.107, issue.1, pp.56-71, 2007.
DOI : 10.1016/j.ygyno.2007.07.043

R. Nishi, Y. Okuda, E. Watanabe, T. Mori, S. Iwai et al., Centrin 2 Stimulates Nucleotide Excision Repair by Interacting with Xeroderma Pigmentosum Group C Protein, Molecular and Cellular Biology, vol.25, issue.13, pp.5664-5674, 2005.
DOI : 10.1128/MCB.25.13.5664-5674.2005

J. Charbonnier, E. Renaud, S. Miron, L. Du, M. Blouquit et al., Structural, Thermodynamic, and Cellular Characterization of Human Centrin 2 Interaction with Xeroderma Pigmentosum Group C Protein, Journal of Molecular Biology, vol.373, issue.4, pp.1032-1046, 2007.
DOI : 10.1016/j.jmb.2007.08.046

B. Shoichet, Virtual screening of chemical libraries, Nature, vol.55, issue.7019, pp.862-865, 2004.
DOI : 10.1093/nar/30.1.255

M. Montes, M. Miteva, and B. Villoutreix, Structure-based virtual ligand screening with LigandFit: Pose prediction and enrichment of compound collections, Proteins: Structure, Function, and Bioinformatics, vol.67, issue.9-10, pp.712-725, 2007.
DOI : 10.1002/prot.21405

B. Villoutreix, R. Eudes, and M. Miteva, Structure-Based Virtual Ligand Screening: Recent Success Stories, Combinatorial Chemistry & High Throughput Screening, vol.12, issue.10, pp.1000-1016, 2009.
DOI : 10.2174/138620709789824682

M. Totrov and R. Abagyan, Flexible ligand docking to multiple receptor conformations: a practical alternative, Current Opinion in Structural Biology, vol.18, issue.2, pp.178-184, 2008.
DOI : 10.1016/j.sbi.2008.01.004

L. Yang, E. Eyal, I. Bahar, and A. Kitao, Principal component analysis of native ensembles of biomolecular structures (PCA_NEST): insights into functional dynamics, Bioinformatics, vol.25, issue.5, pp.606-614, 2009.
DOI : 10.1093/bioinformatics/btp023

X. Barril and S. Morley, Unveiling the Full Potential of Flexible Receptor Docking Using Multiple Crystallographic Structures, Journal of Medicinal Chemistry, vol.48, issue.13, pp.4432-4443, 2005.
DOI : 10.1021/jm048972v

K. Damm and H. Carlson, Exploring Experimental Sources of Multiple Protein Conformations in Structure-Based Drug Design, Journal of the American Chemical Society, vol.129, issue.26, pp.8225-8235, 2007.
DOI : 10.1021/ja0709728

M. Rueda, G. Bottegoni, and R. Abagyan, Recipes for the Selection of Experimental Protein Conformations for Virtual Screening, Journal of Chemical Information and Modeling, vol.50, issue.1, pp.186-193, 2010.
DOI : 10.1021/ci9003943

M. Mangoni, D. Roccatano, D. Nola, and A. , Docking of flexible ligands to flexible receptors in solution by molecular dynamics simulation, Proteins: Structure, Function, and Genetics, vol.28, issue.2, pp.153-162, 1999.
DOI : 10.1002/(SICI)1097-0134(19990501)35:2<153::AID-PROT2>3.0.CO;2-E

J. Lin, A. Perryman, J. Schames, and J. Mccammon, The relaxed complex method: Accommodating receptor flexibility for drug design with an improved scoring scheme, Biopolymers, vol.4, issue.1, pp.47-62, 2003.
DOI : 10.1002/bip.10218

C. Cavasotto, J. Kovacs, and R. Abagyan, Representing Receptor Flexibility in Ligand Docking through Relevant Normal Modes, Journal of the American Chemical Society, vol.127, issue.26, pp.9632-9640, 2005.
DOI : 10.1021/ja042260c

S. Dobbins, V. Lesk, and M. Sternberg, Insights into protein flexibility: The relationship between normal modes and conformational change upon protein-protein docking, Proceedings of the National Academy of Sciences, vol.105, issue.30, pp.10390-10395, 2008.
DOI : 10.1073/pnas.0802496105

O. Sperandio, L. Mouawad, E. Pinto, B. Villoutreix, D. Perahia et al., How to choose relevant multiple receptor conformations for virtual screening: a test case of Cdk2 and normal mode analysis, European Biophysics Journal, vol.18, issue.9, pp.1365-1372, 2010.
DOI : 10.1007/s00249-010-0592-0

G. Bottegoni, I. Kufareva, M. Totrov, and R. Abagyan, Four-Dimensional Docking: A Fast and Accurate Account of Discrete Receptor Flexibility in Ligand Docking, Journal of Medicinal Chemistry, vol.52, issue.2, pp.397-406, 2009.
DOI : 10.1021/jm8009958

E. Bolstad and A. Anderson, In pursuit of virtual lead optimization: The role of the receptor structure and ensembles in accurate docking, Proteins: Structure, Function, and Bioinformatics, vol.45, issue.3, pp.566-580, 2008.
DOI : 10.1002/prot.22081

I. Durussel, Y. Blouquit, S. Middendorp, C. Craescu, and J. Cox, Cation- and peptide-binding properties of human centrin 2, FEBS Letters, vol.240, issue.2-3, pp.208-212, 2000.
DOI : 10.1016/S0014-5793(00)01452-6

J. Thompson, Z. Ryan, J. Salisbury, and R. Kumar, The Structure of the Human Centrin 2-Xeroderma Pigmentosum Group C Protein Complex, Journal of Biological Chemistry, vol.281, issue.27, pp.18746-18752, 2006.
DOI : 10.1074/jbc.M513667200

D. Moustakas, P. Lang, S. Pegg, E. Pettersen, I. Kuntz et al., Development and validation of a modular, extensible docking program: DOCK 5, Journal of Computer-Aided Molecular Design, vol.10, issue.10-11, pp.601-619, 2006.
DOI : 10.1007/s10822-006-9060-4

J. Martinez-sanz, F. Kateb, L. Assairi, Y. Blouquit, G. Bodenhausen et al., Structure, Dynamics and Thermodynamics of the Human Centrin 2/hSfi1 Complex, Journal of Molecular Biology, vol.395, issue.1, pp.191-204, 2010.
DOI : 10.1016/j.jmb.2009.10.041

URL : https://hal.archives-ouvertes.fr/hal-00491354

T. Yuan and H. Vogel, Substitution of the methionine residues of calmodulin with the unnatural amino acid analogs ethionine and norleucine: Biochemical and spectroscopic studies, Protein Science, vol.2, issue.150, pp.113-121, 1999.
DOI : 10.1110/ps.8.1.113

L. Guilloux, V. Schmidtke, P. Tuffery, and P. , Fpocket: An open source platform for ligand pocket detection, BMC Bioinformatics, vol.10, issue.1, p.168, 2009.
DOI : 10.1186/1471-2105-10-168

N. Huang, C. Kalyanaraman, J. Irwin, and M. Jacobson, Physics-Based Scoring of Protein???Ligand Complexes:?? Enrichment of Known Inhibitors in Large-Scale Virtual Screening, Journal of Chemical Information and Modeling, vol.46, issue.1, pp.243-253, 2006.
DOI : 10.1021/ci0502855

T. Pencheva, O. Soumana, I. Pajeva, and M. Miteva, Post-docking virtual screening of diverse binding pockets: Comparative study using DOCK, AMMOS, X-Score and FRED scoring functions, European Journal of Medicinal Chemistry, vol.45, issue.6, pp.2622-2628, 2010.
DOI : 10.1016/j.ejmech.2009.12.025

T. Pencheva, D. Lagorce, I. Pajeva, B. Villoutreix, and M. Miteva, AMMOS: Automated Molecular Mechanics Optimization tool for in silico Screening, BMC Bioinformatics, vol.9, issue.1, p.438, 2008.
DOI : 10.1186/1471-2105-9-438

URL : https://hal.archives-ouvertes.fr/inserm-00668481

C. Cavasotto and R. Abagyan, Protein Flexibility in Ligand Docking and Virtual Screening to Protein Kinases, Journal of Molecular Biology, vol.337, issue.1, pp.209-225, 2004.
DOI : 10.1016/j.jmb.2004.01.003

D. Thompson, C. Humblet, and D. Joseph-mccarthy, Investigation of MM-PBSA Rescoring of Docking Poses, Journal of Chemical Information and Modeling, vol.48, issue.5, pp.1081-1091, 2008.
DOI : 10.1021/ci700470c

H. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. Bhat et al., The Protein Data Bank, Nucleic Acids Research, vol.28, issue.1, pp.235-242, 2000.
DOI : 10.1093/nar/28.1.235

R. Chattopadhyaya, W. Meador, A. Means, and F. Quiocho, Calmodulin structure refined at 1.7 ?? resolution, Journal of Molecular Biology, vol.228, issue.4, pp.1177-1192, 1992.
DOI : 10.1016/0022-2836(92)90324-D

J. Gsponer, J. Christodoulou, A. Cavalli, J. Bui, B. Richter et al., A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction, Structure, vol.16, issue.5, pp.736-746, 2008.
DOI : 10.1016/j.str.2008.02.017

M. Miteva, P. Tuffery, and B. Villoutreix, PCE: web tools to compute protein continuum electrostatics, Nucleic Acids Research, vol.33, issue.Web Server, pp.372-375, 2005.
DOI : 10.1093/nar/gki365

E. Pettersen, T. Goddard, C. Huang, G. Couch, D. Greenblatt et al., UCSF Chimera?A visualization system for exploratory research and analysis, Journal of Computational Chemistry, vol.373, issue.13, pp.1605-1612, 2004.
DOI : 10.1002/jcc.20084

N. Sauton, D. Lagorce, B. Villoutreix, and M. Miteva, MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening, BMC Bioinformatics, vol.9, issue.1, p.184, 2008.
DOI : 10.1186/1471-2105-9-184

R. Desjarlais, R. Sheridan, G. Seibel, J. Dixon, I. Kuntz et al., Using shape complementarity as an initial screen in designing ligands for a receptor binding site of known three-dimensional structure, Journal of Medicinal Chemistry, vol.31, issue.4, pp.722-729, 1988.
DOI : 10.1021/jm00399a006

D. Lagorce, T. Pencheva, B. Villoutreix, and M. Miteva, DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening, BMC Chemical Biology, vol.9, issue.1, p.6, 2009.
DOI : 10.1186/1472-6769-9-6

URL : https://hal.archives-ouvertes.fr/inserm-00668481

J. Srinivasan, T. Cheatham, P. Cieplak, P. Kollman, and D. Case, Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate???DNA Helices, Journal of the American Chemical Society, vol.120, issue.37, pp.9401-9409, 1998.
DOI : 10.1021/ja981844+

R. Wang, L. Lai, and S. Wang, Further development and validation of empirical scoring functions for structure-based binding affinity prediction, Journal of Computer-Aided Molecular Design, vol.16, issue.1, pp.11-26, 2002.
DOI : 10.1023/A:1016357811882

W. Delano, The PyMOL Molecular Graphics System, DeLano Scientific, 2002.