mCSM-PPI2: predicting the effects of mutations on protein-protein interactions.

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Rodrigues, Carlos HM 
Myung, Yoochan 
Pires, Douglas EV 
Ascher, David B 

Protein-protein Interactions are involved in most fundamental biological processes, with disease causing mutations enriched at their interfaces. Here we present mCSM-PPI2, a novel machine learning computational tool designed to more accurately predict the effects of missense mutations on protein-protein interaction binding affinity. mCSM-PPI2 uses graph-based structural signatures to model effects of variations on the inter-residue interaction network, evolutionary information, complex network metrics and energetic terms to generate an optimised predictor. We demonstrate that our method outperforms previous methods, ranking first among 26 others on CAPRI blind tests. mCSM-PPI2 is freely available as a user friendly webserver at

Benchmarking, Binding Sites, Crystallography, X-Ray, Datasets as Topic, Humans, Internet, Machine Learning, Mutation, Missense, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Proteins, Software, Thermodynamics
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Nucleic Acids Res
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Oxford University Press (OUP)
This work was supported by the Australian Government Research Training Program Scholarship [to C.H.M.R and Y.M.]; the Jack Brockhoff Foundation [JBF 4186, 2016 to D.B.A.]; a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council (MRC) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) [MR/M026302/1 to D.B.A. and D.E.V.P.]; the National Health and Medical Research Council of Australia [APP1072476 to D.B.A.]; the Victorian Life Sciences Computation Initiative (VLSCI), an initiative of the Victorian Government, Australia, on its Facility hosted at the University of Melbourne [UOM0017]; the Instituto René Rachou (IRR/FIOCRUZ Minas), Brazil and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [to D.E.V.P.] and the Department of Biochemistry and Molecular Biology, University of Melbourne [to D.B.A.]. Supported in part by the Victorian Government's OIS Program.