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Here we present mCSM-PPI2, a novel machine learning computational tool designed to more accurately predict the effects of missense mutations on protein\u2013protein 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 http:\/\/biosig.unimelb.edu.au\/mcsm_ppi2\/.<\/jats:p>","DOI":"10.1093\/nar\/gkz383","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T19:18:23Z","timestamp":1558379903000},"page":"W338-W344","source":"Crossref","is-referenced-by-count":338,"title":["mCSM-PPI2: predicting the effects of mutations on protein\u2013protein interactions"],"prefix":"10.1093","volume":"47","author":[{"given":"Carlos H M","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne,\u00a0Australia"},{"name":"ACRF Facility for Innovative Cancer Drug Discovery, Bio21 Institute, University of Melbourne,\u00a0Melbourne, Australia"},{"name":"Structural Biology and Bioinformatics, Baker Heart and Diabetes Institute, Melbourne, Australia"}]},{"given":"Yoochan","family":"Myung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne,\u00a0Australia"},{"name":"ACRF Facility for Innovative Cancer Drug Discovery, Bio21 Institute, University of Melbourne,\u00a0Melbourne, Australia"},{"name":"Structural Biology and Bioinformatics, Baker Heart and Diabetes Institute, Melbourne, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3004-2119","authenticated-orcid":false,"given":"Douglas E V","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne,\u00a0Australia"},{"name":"ACRF Facility for Innovative Cancer Drug Discovery, Bio21 Institute, University of Melbourne,\u00a0Melbourne, Australia"},{"name":"Structural Biology and Bioinformatics, Baker Heart and Diabetes Institute, Melbourne, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-2413","authenticated-orcid":false,"given":"David B","family":"Ascher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne,\u00a0Australia"},{"name":"ACRF Facility for Innovative Cancer Drug Discovery, Bio21 Institute, University of Melbourne,\u00a0Melbourne, Australia"},{"name":"Structural Biology and Bioinformatics, Baker Heart and Diabetes Institute, Melbourne, Australia"},{"name":"Department of Biochemistry, University of Cambridge,\u00a0Cambridge, UK"}]}],"member":"286","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"key":"2019062808225253000_B1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ygeno.2007.12.007","article-title":"A protein\u2013protein interaction network of transcription factors acting during liver cell proliferation","volume":"91","author":"Gao","year":"2008","journal-title":"Genomics"},{"key":"2019062808225253000_B2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1385\/MB:29:1:57","article-title":"Protein-protein interactions in the regulation of the extracellular signal-regulated kinase","volume":"29","author":"Chuderland","year":"2005","journal-title":"Mol. 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