A. Gavin, P. Aloy, P. Grandi, R. Krause, M. Boesche et al., Proteome survey reveals modularity of the yeast cell machinery, Superti-Furga, Proteome survey reveals modularity of the yeast cell machinery, pp.631-636, 2006.
DOI : 10.1534/genetics.104.040063

J. J. Gray, High-resolution protein???protein docking, Current Opinion in Structural Biology, vol.16, issue.2, pp.183-193, 2006.
DOI : 10.1016/j.sbi.2006.03.003

R. Grünberg, J. Leckner, and M. Nilges, Complementarity of Structure Ensembles in Protein-Protein Binding, Structure, vol.12, issue.12, pp.2125-2136, 2004.
DOI : 10.1016/j.str.2004.09.014

R. Grünberg, M. Nilges, and J. Leckner, Flexibility and Conformational Entropy in Protein-Protein Binding, Structure, vol.14, issue.4, pp.683-693, 2006.
DOI : 10.1016/j.str.2006.01.014

C. Chotia and J. Janin, Principles of protein???protein recognition, Nature, vol.71, issue.5520, pp.705-708, 1975.
DOI : 10.1038/256705a0

J. K. Kouadio, J. R. Horn, G. Pal, and A. A. Kossiakoff, Shotgun Alanine Scanning Shows That Growth Hormone Can Bind Productively to Its Receptor through a Drastically Minimized Interface, Journal of Biological Chemistry, vol.280, issue.27, pp.25524-25532, 2005.
DOI : 10.1074/jbc.M502167200

S. Jones and J. Thornton, Analysis of protein-protein interaction sites using surface patches, Journal of Molecular Biology, vol.272, issue.1
DOI : 10.1006/jmbi.1997.1234

B. Ma, T. Elkayam, H. Wolfson, and R. Nussinov, Protein-protein interactions: Structurally conserved residues distinguish between binding sites and exposed protein surfaces, Proceedings of the National Academy of Sciences, vol.100, issue.10, pp.5772-5777, 2003.
DOI : 10.1073/pnas.1030237100

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC156276

L. Lo-conte, C. Chothia, and J. Janin, The atomic structure of protein-protein recognition sites, Journal of Molecular Biology, vol.2852, pp.2177-2198, 1999.

S. A. Teichmann, Principles of protein-protein interactions, Bioinformatics, vol.18, issue.Suppl 2, p.249, 2002.
DOI : 10.1093/bioinformatics/18.suppl_2.S249

T. Clackson and J. Wells, A hot spot of binding energy in a hormone-receptor interface, Science, vol.267, issue.5196, pp.383-386, 1995.
DOI : 10.1126/science.7529940

I. S. Moreira, P. A. Fernandes, and M. J. Ramos, Hot spots ? a review of the proteinprotein interface determinant amino-acid residues, Proteins: Structure, Function, and Bioinformatics, vol.68, issue.4

D. Reichmann, O. Rahat, S. Albeck, R. Meged, O. Dym et al., From The Cover: The modular architecture of protein-protein binding interfaces, Proceedings of the National Academy of Sciences, vol.102, issue.1, pp.57-62, 2005.
DOI : 10.1073/pnas.0407280102

D. Reichmann, O. Rahat, M. Cohen, H. Neuvirth, and G. Schreiber, The molecular architecture of protein???protein binding sites, Current Opinion in Structural Biology, vol.17, issue.1, pp.67-76, 2007.
DOI : 10.1016/j.sbi.2007.01.004

D. R. Caffrey, S. Somaroo, J. D. Hughes, J. Mintseris, and E. S. Huang, Are protein-protein interfaces more conserved in sequence than the rest of the protein surface?, Protein Science, vol.13, issue.1, pp.190-202, 2004.
DOI : 10.1110/ps.03323604

B. E. Shakhnovich, N. V. Dokholyan, C. Delisi, and E. I. Shakhnovich, Functional Fingerprints of Folds: Evidence for Correlated Structure???Function Evolution, Journal of Molecular Biology, vol.326, issue.1, pp.1-9, 2003.
DOI : 10.1016/S0022-2836(02)01362-1

A. Valencia, Automatic annotation of protein function, Current Opinion in Structural Biology, vol.15, issue.3, pp.267-274, 2005.
DOI : 10.1016/j.sbi.2005.05.010

P. Aloy, H. Ceulemans, A. Stark, and R. B. Russell, The Relationship Between Sequence and Interaction Divergence in Proteins, Journal of Molecular Biology, vol.332, issue.5, pp.989-998, 2003.
DOI : 10.1016/j.jmb.2003.07.006

R. P. Bahadur, P. Chakrabarti, F. Rodier, and J. Janin, A Dissection of Specific and Non-specific Protein???Protein Interfaces, Journal of Molecular Biology, vol.336, issue.4, pp.943-955, 2004.
DOI : 10.1016/j.jmb.2003.12.073

O. Lichtarge, H. R. Bourne, and F. E. Cohen, An Evolutionary Trace Method Defines Binding Surfaces Common to Protein Families, Journal of Molecular Biology, vol.257, issue.2, pp.342-358, 1996.
DOI : 10.1006/jmbi.1996.0167

O. Rahat, A. Yitzhaky, and G. Schreiber, Cluster conservation as a novel tool for studying protein-protein interactions evolution, Proteins. URL http
DOI : 10.1002/prot.21749

F. Rodier, R. Bahadur, P. Chakrabarti, and J. Janin, Hydration of protein-protein interfaces, Proteins: Structure, Function, and Bioinformatics, vol.280, issue.1, pp.36-45, 2005.
DOI : 10.1002/prot.20478

A. A. Bogan and K. S. Thorn, Anatomy of hot spots in protein interfaces, Journal of Molecular Biology, vol.280, issue.1, pp.1-9, 1998.
DOI : 10.1006/jmbi.1998.1843

A. Fernandez and R. S. Berry, Extent of Hydrogen-Bond Protection in Folded Proteins: A Constraint on Packing Architectures, Biophysical Journal, vol.83, issue.5, pp.2475-2481, 2002.
DOI : 10.1016/S0006-3495(02)75258-2

A. Fernandez and H. A. Scheraga, Insufficiently dehydrated hydrogen bonds as determinants of protein interactions, Proceedings of the National Academy of Sciences, vol.100, issue.1, pp.113-118, 2003.
DOI : 10.1073/pnas.0136888100

I. Mihalek, I. Res, and O. Lichtarge, On Itinerant Water Molecules and Detectability of Protein???Protein Interfaces through Comparative Analysis of Homologues, Journal of Molecular Biology, vol.369, issue.2, pp.584-595, 2007.
DOI : 10.1016/j.jmb.2007.03.057

F. Cazals, F. Proust, R. P. Bahadur, and J. Janin, Revisiting the Voronoi description of protein-protein interfaces, Protein Science, vol.15, issue.9, pp.2082-2092, 2006.
DOI : 10.1110/ps.062245906

URL : https://hal.archives-ouvertes.fr/hal-00796062

F. M. Richards, The interpretation of protein structures: Total volume, group volume distributions and packing density, Journal of Molecular Biology, vol.82, issue.1, pp.1-14, 1974.
DOI : 10.1016/0022-2836(74)90570-1

F. Aurenhammer, Power Diagrams: Properties, Algorithms and Applications, SIAM Journal on Computing, vol.16, issue.1, pp.78-96, 1987.
DOI : 10.1137/0216006

C. Chotia, The nature of the accessible and buried surfaces in proteins, Journal of Molecular Biology, vol.105, issue.1, pp.1-12, 1976.
DOI : 10.1016/0022-2836(76)90191-1

B. Lee and F. M. Richards, The interpretation of protein structures: Estimation of static accessibility, Journal of Molecular Biology, vol.55, issue.3, pp.379-380, 1971.
DOI : 10.1016/0022-2836(71)90324-X

H. Edelsbrunner and E. P. Mücke, Three-dimensional alpha shapes, ACM Transactions on Graphics, vol.13, issue.1, pp.43-72, 1994.
DOI : 10.1145/174462.156635

URL : http://arxiv.org/abs/math/9410208

R. D. Finn, J. Mistry, B. Schuster-bockler, S. Griffiths-jones, V. Hollich et al., Pfam: clans, web tools and services, Pfam: clans, web tools and services, pp.247-251, 2006.
DOI : 10.1093/nar/gkj149

R. Durbin, S. Eddy, A. Krogh, and G. Mitchison, Biological sequence analysis: probabilistic models of proteins and nucleic acids, 1998.
DOI : 10.1017/CBO9780511790492

K. Wang and R. Samudrala, Incorporating background frequency improves entropy-based residue conservation measures, BMC Bioinformatics, vol.7, issue.385, pp.1471-2105, 2006.

M. Guharoy and P. Chakrabarti, Conservation and relative importance of residues across protein-protein interfaces, Proceedings of the National Academy of Sciences, vol.102, issue.43, pp.15447-15452, 2005.
DOI : 10.1073/pnas.0505425102

T. Selzer and G. Schreiber, Predicting the rate enhancement of protein complex formation from the electrostatic energy of interaction11Edited by B. Honig, Journal of Molecular Biology, vol.287, issue.2, pp.409-419, 1999.
DOI : 10.1006/jmbi.1999.2615

N. Ostermann, I. Schlichting, R. Brundiers, M. Konrad, J. Reinstein et al., Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate, Structure, vol.8, issue.6, pp.629-642
DOI : 10.1016/S0969-2126(00)00149-0

Y. A. Ban, H. Edelsbrunner, and J. Rudolph, Interface surfaces for protein-protein complexes, pp.205-212, 2004.

R. R. Gabdoulline, R. C. Wade, and D. Walther, MolSurfer: a macromolecular interface navigator, Nucleic Acids Research, vol.31, issue.13, pp.3349-3351, 2003.
DOI : 10.1093/nar/gkg588

URL : http://doi.org/10.1093/nar/gkg588

A. Poupon, Voronoi and Voronoi-related tessellations in studies of protein structure and interaction, Current Opinion in Structural Biology, vol.14, issue.2, pp.233-241, 2004.
DOI : 10.1016/j.sbi.2004.03.010

S. Chakravarty and R. Varadarajan, Residue depth: a novel parameter for the analysis of protein structure and stability, Structure, vol.7, issue.7, pp.723-732, 1999.
DOI : 10.1016/S0969-2126(99)80097-5

A. Pintar, O. Carugo, and S. Pongor, Atom depth in protein structure and function, Trends in Biochemical Sciences, vol.28, issue.11, pp.593-597, 2003.
DOI : 10.1016/j.tibs.2003.09.004

A. Pintar, O. Carugo, and S. Pongor, Atom Depth as a Descriptor of the Protein Interior, Biophysical Journal, vol.84, issue.4, pp.2553-2561, 2003.
DOI : 10.1016/S0006-3495(03)75060-7

P. Chakrabarti and J. Janin, Dissecting protein-protein recognition sites, Proteins: Structure, Function, and Genetics, vol.11, issue.3
DOI : 10.1002/prot.10085

I. M. Nooren and J. M. Thornton, Structural Characterisation and Functional Significance of Transient Protein???Protein Interactions, Journal of Molecular Biology, vol.325, issue.5, pp.991-1018, 2003.
DOI : 10.1016/S0022-2836(02)01281-0

A. Bordner and R. Abagyan, Statistical analysis and prediction of protein-protein interfaces, Proteins: Structure, Function, and Bioinformatics, vol.263, issue.3, pp.353-66, 2005.
DOI : 10.1002/prot.20433

J. G. Sheldon and . Park, Statistical and molecular dynamics studies of buried waters in globular proteins, Proteins: Structure, Function, and Bioinformatics, vol.60, pp.450-463, 2005.

B. Brooks, R. Bruccoleri, B. D. Olafson, D. States, S. Swaminathan et al., CHARMM: A program for macromolecular energy, minimization, and dynamics calculations, Journal of Computational Chemistry, vol.I, issue.2, pp.187-217, 1983.
DOI : 10.1002/jcc.540040211

P. Steinbach, R. Loncharich, and B. Brooks, The effects of environment and hydration on protein dynamics: A simulation study of myoglobin, Chemical Physics, vol.158, issue.2-3, pp.383-94, 1991.
DOI : 10.1016/0301-0104(91)87078-A

R. Grünberg, M. Nilges, and J. Leckner, Biskit A software platform for structural bioinformatics, Bioinformatics, vol.23, issue.6, pp.769-770, 2007.
DOI : 10.1093/bioinformatics/btl655

D. V. Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark et al., GROMACS: Fast, flexible, and free, Journal of Computational Chemistry, vol.26, issue.16, pp.1701-1718, 2005.
DOI : 10.1002/jcc.20291

W. Damm, A. Frontera, J. Tirado-rives, and W. L. Jorgensen, Opls all-atom force field for carbohydrates, 16<1955:: AID-JCC1>3.0.CO, pp.1096-987, 1955.

D. M. Green and J. M. Swets, Signal detection theory and psychophysics, 1966.

M. Zweig and G. Campbell, Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine [published erratum appears in, Clin Chem, 1993.

W. Delano, The Pymol molecular graphics system, 2002.

O. Cheong, The Ipe extensible drawing editor, 1993.

. Unité-de-recherche-inria-sophia and . Antipolis, route des Lucioles -BP 93 -06902 Sophia Antipolis Cedex (France) Unité de recherche INRIA Futurs : Parc Club Orsay Université -ZAC des Vignes 4, 2004.

I. Unité-de-recherche and . Lorraine, Technopôle de Nancy-Brabois -Campus scientifique 615, rue du Jardin Botanique -BP 101 -54602 Villers-lès-Nancy Cedex (France) Unité de recherche INRIA Rennes : IRISA, Campus universitaire de Beaulieu -35042 Rennes Cedex (France) Unité de recherche INRIA Rhône-Alpes : 655, avenue de l'Europe -38334 Montbonnot Saint-Ismier (France) Unité de recherche INRIA Rocquencourt, Domaine de Voluceau -Rocquencourt -BP 105 -78153 Le Chesnay Cedex

I. De-voluceau-rocquencourt, BP 105 -78153 Le Chesnay Cedex (France) http://www.inria.fr ISSN, pp.249-6399