title: A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces.
abstract: Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model is trained on a large number of complexes and on a significantly larger number of different structural- and evolutionary sequence-based features. In particular, we added interface size, type of interaction between residues at the interface of the complex, number of different types of residues at the interface and the Position-Specific Scoring Matrix (PSSM), for a total of 79 features. We used twenty-seven algorithms from a simple linear-based function to support-vector machine models with different cost functions. The best model was achieved by the use of the conditional inference random forest (c-forest) algorithm with a dataset pre-processed by the normalization of features and with up-sampling of the minor class. The method has an overall accuracy of 0.80, an F1-score of 0.73, a sensitivity of 0.76 and a specificity of 0.82 for the independent test set.
authors.affiliation: Centro de Ci&#234;ncias e Tecnologias Nucleares, Instituto Superior T&#233;cnico, Universidade de Lisboa, Estrada Nacional 10 (ao km 139,7), 2695-066 Bobadela LRS, Portugal. ritamelo@ctn.ist.utl.pt.|CNC-Center for Neuroscience and Cell Biology; Rua Larga, Faculdade de Medicina, Polo I, 1ºandar, Universidade de Coimbra, 3004-504 Coimbra, Portugal. ritamelo@ctn.ist.utl.pt.
authors.forename: Rita
authors.initials: R
authors.lastname: Melo
authors.affiliation: Department of Genetics and Genomics and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. robert.fieldhouse@mssm.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Fieldhouse
authors.affiliation: REQUIMTE (Rede de Qu&#237;mica e Tecnologia), Faculdade de Ci&#234;ncias da Universidade do Porto, Departamento de Qu&#237;mica e Bioqu&#237;mica, Rua do Campo Alegre, 4169-007 Porto, Portugal. asmelo@fc.up.pt.
authors.forename: André
authors.initials: A
authors.lastname: Melo
authors.affiliation: Centro de Ci&#234;ncias e Tecnologias Nucleares, Instituto Superior T&#233;cnico, Universidade de Lisboa, Estrada Nacional 10 (ao km 139,7), 2695-066 Bobadela LRS, Portugal. jgalamba@ctn.tecnico.ulisboa.pt.
authors.forename: João D G
authors.initials: JD
authors.lastname: Correia
authors.affiliation: REQUIMTE (Rede de Qu&#237;mica e Tecnologia), Faculdade de Ci&#234;ncias da Universidade do Porto, Departamento de Qu&#237;mica e Bioqu&#237;mica, Rua do Campo Alegre, 4169-007 Porto, Portugal. ncordeir@fc.up.pt.
authors.forename: Maria Natália D S
authors.initials: MN
authors.lastname: Cordeiro
authors.affiliation: Department of Genetics and Genomics and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. zeynep.gumus@gmail.com.
authors.forename: Zeynep H
authors.initials: ZH
authors.lastname: Gümüş
authors.affiliation: CMUP/FCUP, Centro de Matem&#225;tica da Universidade do Porto, Faculdade de Ci&#234;ncias, Rua do Campo Alegre, 4169-007 Porto, Portugal. Jpcosta@fc.up.pt.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Costa
authors.affiliation: Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Utrecht 3584CH, The Netherlands. a.m.j.j.bonvin@uu.nl.
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
authors.affiliation: CNC-Center for Neuroscience and Cell Biology; Rua Larga, Faculdade de Medicina, Polo I, 1ºandar, Universidade de Coimbra, 3004-504 Coimbra, Portugal. irina.moreira@cnc.uc.pt.|Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry, Utrecht University, Utrecht 3584CH, The Netherlands. irina.moreira@cnc.uc.pt.
authors.forename: Irina S
authors.initials: IS
authors.lastname: Moreira
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D000069550:Machine Learning; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins
keywords: Solvent Accessible Surface Area (SASA); evolutionary sequence conservation; hot-spots; machine learning; protein-protein interfaces