title: i-Patch: interprotein contact prediction using local network information.
abstract: Biological processes are commonly controlled by precise protein-protein interactions. These connections rely on specific amino acids at the binding interfaces. Here we predict the binding residues of such interprotein complexes. We have developed a suite of methods, i-Patch, which predict the interprotein contact sites by considering the two proteins as a network, with residues as nodes and contacts as edges. i-Patch starts with two proteins, A and B, which are assumed to interact, but for which the structure of the complex is not available. However, we assume that for each protein, we have a reference structure and a multiple sequence alignment of homologues. i-Patch then uses the propensities of patches of residues to interact, to predict interprotein contact sites. i-Patch outperforms several other tested algorithms for prediction of interprotein contact sites. It gives 59% precision with 20% recall on a blind test set of 31 protein pairs. Combining the i-Patch scores with an existing correlated mutation algorithm, McBASC, using a logistic model gave little improvement. Results from a case study, on bacterial chemotaxis protein complexes, demonstrate that our predictions can identify contact residues, as well as suggesting unknown interfaces in multiprotein complexes.
authors.affiliation: Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hamer
authors.forename: Qiang
authors.initials: Q
authors.lastname: Luo
authors.forename: Judith P
authors.initials: JP
authors.lastname: Armitage
authors.forename: Gesine
authors.initials: G
authors.lastname: Reinert
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Deane
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D011506:Proteins