{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T04:24:29Z","timestamp":1770351869090,"version":"3.49.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Large-scale experiments reveal pairs of interacting proteins but leave the residues involved in the interactions unknown. These interface residues are essential for understanding the mechanism of interaction and are often desired drug targets. Reliable identification of residues that reside in protein\u2013protein interface typically requires analysis of protein structure. Therefore, for the vast majority of proteins, for which there is no high-resolution structure, there is no effective way of identifying interface residues.<\/jats:p><jats:p>Results: Here we present a machine learning-based method that identifies interacting residues from sequence alone. Although the method is developed using transient protein\u2013protein interfaces from complexes of experimentally known 3D structures, it never explicitly uses 3D information. Instead, we combine predicted structural features with evolutionary information. The strongest predictions of the method reached over 90% accuracy in a cross-validation experiment. Our results suggest that despite the significant diversity in the nature of protein\u2013protein interactions, they all share common basic principles and that these principles are identifiable from sequence alone.<\/jats:p><jats:p>Contact: \u00a0yanay.ofran@columbia.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btl303","type":"journal-article","created":{"date-parts":[[2007,1,19]],"date-time":"2007-01-19T18:51:12Z","timestamp":1169232672000},"page":"e13-e16","source":"Crossref","is-referenced-by-count":217,"title":["ISIS: interaction sites identified from sequence"],"prefix":"10.1093","volume":"23","author":[{"given":"Yanay","family":"Ofran","sequence":"first","affiliation":[{"name":"CUBIC & North-East Structural Genomics Consortium, Department of Biochemistry and Molecular Biophysics, Columbia University 1 \u00a0 1 \u00a0 \u00a0 630 West 168th Street, New York, NY 10032, USA"},{"name":"Columbia University Center for Computational Biology and Bioinformatics (C2B2), 1130 St Nicholas Avenue 2 \u00a0 2 \u00a0 \u00a0 Rm 801, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhard","family":"Rost","sequence":"additional","affiliation":[{"name":"CUBIC & North-East Structural Genomics Consortium, Department of Biochemistry and Molecular Biophysics, Columbia University 1 \u00a0 1 \u00a0 \u00a0 630 West 168th Street, New York, NY 10032, USA"},{"name":"Columbia University Center for Computational Biology and Bioinformatics (C2B2), 1130 St Nicholas Avenue 2 \u00a0 2 \u00a0 \u00a0 Rm 801, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,1,15]]},"reference":[{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1073\/pnas.092147999","article-title":"Interrogating protein interaction networks through structural biology","volume":"99","author":"Aloy","year":"2002","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped Blast and PSI-Blast: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1006\/jmbi.2000.4474","article-title":"ConSurf: an algorithmic tool for the identification of functional regions in proteins by surface mapping of phylogenetic information","volume":"307","author":"Armon","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/nar\/28.1.45","article-title":"The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000","volume":"28","author":"Bairoch","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1107\/S0907444902003451","article-title":"The Protein Data Bank","volume":"58","author":"Berman","year":"2002","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0022-2836(77)80200-3","article-title":"The Protein Data Bank: a computer-based archival file for macromolecular structures","volume":"112","author":"Bernstein","year":"1977","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0014-5793(88)81066-4","article-title":"Protein secondary structure and homology by neural networks","volume":"241","author":"Bohr","year":"1988","journal-title":"FEBS Lett."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0014-5793(90)80632-S","article-title":"A novel approach to prediction of the 3-dimensional structures of protein backbones by neural networks","volume":"261","author":"Bohr","year":"1990","journal-title":"FEBS Lett."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1046\/j.1432-1033.2002.02767.x","article-title":"Prediction of protein\u2013protein interaction sites in heterocomplexes with neural networks","volume":"269","author":"Fariselli","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/prot.20285","article-title":"Optimal docking area: a new method for predicting protein\u2013protein interaction sites","volume":"58","author":"Fernandez-Recio","year":"2005","journal-title":"Proteins"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/bioinformatics\/15.9.759","article-title":"Finding families for genomic ORFans","volume":"15","author":"Fischer","year":"1999","journal-title":"Bioinformatics"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/415141a","article-title":"Functional organization of the yeast proteome by systematic analysis of protein complexes","volume":"415","author":"Gavin","year":"2002","journal-title":"Nature"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1126\/science.1090289","article-title":"A protein interaction map of Drosophila melanogaster","volume":"302","author":"Giot","year":"2003","journal-title":"Science"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/415180a","article-title":"Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry","volume":"415","author":"Ho","year":"2002","journal-title":"Nature"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1073\/pnas.93.1.13","article-title":"Principles of protein\u2013protein interactions","volume":"93","author":"Jones","year":"1996","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1006\/jmbi.1997.1233","article-title":"Prediction of protein\u2013protein interaction sites using patch analysis","volume":"272","author":"Jones","year":"1997","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1093\/protein\/gzh020","article-title":"Prediction of protein\u2013protein interaction sites using support vector machines","volume":"17","author":"Koike","year":"2004","journal-title":"Protein Eng. Des. Sel."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1126\/science.1091403","article-title":"A map of the interactome network of the metazoan C. elegans","volume":"303","author":"Li","year":"2004","journal-title":"Science"},{"key":"2023041107140262900_","author":"Mika","year":"2006"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1110\/ps.0207402","article-title":"Sequence conserved for subcellular localization","volume":"11","author":"Nair","year":"2002","journal-title":"Prot. Sci."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jmb.2004.02.040","article-title":"ProMate: a structure based prediction program to identify the location of protein\u2013protein binding sites","volume":"338","author":"Neuvirth","year":"2004","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0022-2836(02)01223-8","article-title":"Analysing six types of protein\u2013protein interfaces","volume":"325","author":"Ofran","year":"2003","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/S0014-5793(03)00456-3","article-title":"Predicted protein\u2013protein interaction sites from local sequence information","volume":"544","author":"Ofran","year":"2003","journal-title":"FEBS Lett."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/prot.10074","article-title":"In silico two-hybrid system for the selection of physically interacting protein pairs","volume":"47","author":"Pazos","year":"2002","journal-title":"Proteins"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/0022-2836(88)90564-5","article-title":"Predicting the secondary structure of globular proteins using neural network models","volume":"202","author":"Qian","year":"1988","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1093\/bioinformatics\/bti340","article-title":"An evolution based classifier for prediction of protein interfaces without using protein structures","volume":"21","author":"Res","year":"2005","journal-title":"Bioinformatics"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/protein\/12.2.85","article-title":"Twilight zone of protein sequence alignments","volume":"12","author":"Rost","year":"1999","journal-title":"Prot. Eng."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0022-2836(02)00016-5","article-title":"Enzyme function less conserved than anticipated","volume":"318","author":"Rost","year":"2002","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","first-page":"559","article-title":"Prediction in 1D: secondary structure, membrane helices, and accessibility","volume-title":"Structural Bioinformatics","author":"Rost","year":"2002"},{"key":"2023041107140262900_","article-title":"How to use protein 1D structure predicted by PROFphd","author":"Rost","year":"2004","journal-title":"Meth. Mol. Biol"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1006\/jmbi.1993.1413","article-title":"Prediction of protein secondary structure at better than 70% accuracy","volume":"232","author":"Rost","year":"1993","journal-title":"J. Mol. Biol."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1007\/s00018-003-3114-8","article-title":"Automatic prediction of protein function","volume":"60","author":"Rost","year":"2003","journal-title":"Cell Mol. Life Sci."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/prot.340090107","article-title":"Database of homology-derived structures and the structural meaning of sequence alignment","volume":"9","author":"Sander","year":"1991","journal-title":"Proteins"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/nar\/24.1.201","article-title":"The HSSP database of protein structure-sequence alignments","volume":"24","author":"Schneider","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/35001009","article-title":"A comprehensive analysis of protein\u2013protein interactions in Saccharomyces cerevisiae","volume":"403","author":"Uetz","year":"2000","journal-title":"Nature"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.febslet.2005.11.081","article-title":"Predicting protein interaction sites from residue spatial sequence profile and evolution rate","volume":"580","author":"Wang","year":"2005","journal-title":"FEBS Lett"},{"key":"2023041107140262900_","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.sbi.2004.02.003","article-title":"Prediction of protein\u2013protein interactions: the CAPRI experiment, its evaluation and implications","volume":"14","author":"Wodak","year":"2004","journal-title":"Curr. Opin. Struct. Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/2\/e13\/49820346\/bioinformatics_23_2_e13.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/23\/2\/e13\/49820346\/bioinformatics_23_2_e13.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T09:38:48Z","timestamp":1707557928000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/23\/2\/e13\/202238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1,15]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,1,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btl303","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2007,1,15]]},"published":{"date-parts":[[2007,1,15]]}}}