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Cluster conservation as a novel tool for studying protein–protein interactions evolution
Author(s) -
Rahat Ofer,
Yitzhaky Assif,
Schreiber Gideon
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21749
Subject(s) - modularity (biology) , protein superfamily , computational biology , context (archaeology) , protein–protein interaction , biology , protein family , protein engineering , homologous chromosome , protein structure , serine protease , interface (matter) , computer science , genetics , protease , biochemistry , enzyme , paleontology , pulmonary surfactant , gibbs isotherm , gene
Protein–protein interactions networks has come to be a buzzword associated with nets containing edges that represent a pair of interacting proteins (e.g. hormone‐receptor, enzyme‐inhibitor, antigen‐antibody, and a subset of multichain biological machines). Yet, each such interaction composes its own unique network, in which vertices represent amino acid residues, and edges represent atomic contacts. Recent studies have shown that analyses of the data encapsulated in these detailed networks may impact predictions of structure–function correlation. Here, we study homologous families of protein–protein interfaces, which share the same fold but vary in sequence. In this context, we address what properties of the network are shared among relatives with different sequences (and hence different atomic interactions) and which are not. Herein, we develop the general mathematical framework needed to compare the modularity of homologous networks. We then apply this analysis to the structural data of a few interface families, including hemoglobin α–β, growth hormone‐receptor, and Serine protease‐inhibitor. Our results suggest that interface modularity is an evolutionarily conserved property. Hence, protein–protein interfaces can be clustered down to a few modules, with the boundaries being evolutionarily conserved along homologous complexes. This suggests that protein engineering of protein–protein binding sites may be simplified by varying each module, but retaining the overall modularity of the interface. Proteins 2008. © 2007 Wiley‐Liss, Inc.