{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:36:13Z","timestamp":1777462573759,"version":"3.51.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Proteins execute and coordinate cellular functions by interacting with other biomolecules. Among these interactions, protein\u2013protein (including peptide-mediated), protein\u2013DNA and protein\u2013RNA interactions cover a wide range of critical processes and cellular functions. The functional characterization of proteins requires the description and mapping of functional biomolecular interactions and the identification and characterization of functional sites is an important step towards this end.<\/jats:p>\n               <jats:p>Results: We have developed a novel computational method, Multi-VORFFIP (MV), a tool to predicts protein-, peptide-, DNA- and RNA-binding sites in proteins. MV utilizes a wide range of structural, evolutionary, experimental and energy-based information that is integrated into a common probabilistic framework by means of a Random Forest ensemble classifier. While remaining competitive when compared with current methods, MV is a centralized resource for the prediction of functional sites and is interfaced by a powerful web application tailored to facilitate the use of the method and analysis of predictions to non-expert end-users.<\/jats:p>\n               <jats:p>Availability: \u00a0http:\/\/www.bioinsilico.org\/MVORFFIP<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <jats:p>Contact: \u00a0naf4@aber.ac.uk; narcis.fernandez@gmail.com<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts269","type":"journal-article","created":{"date-parts":[[2012,5,5]],"date-time":"2012-05-05T09:09:30Z","timestamp":1336208970000},"page":"1845-1850","source":"Crossref","is-referenced-by-count":32,"title":["A holistic <i>in silico<\/i> approach to predict functional sites in protein structures"],"prefix":"10.1093","volume":"28","author":[{"given":"Joan","family":"Segura","sequence":"first","affiliation":[{"name":"1 Leeds Institute of Molecular Medicine, Section of Experimental Therapeutics, 2Leeds Institute of Molecular Medicine, Section of Molecular Gastroenterology, St. James's University Hospital, University of Leeds. Leeds, LS9 7TF and 3Institute of Biological, Environmental and Rural Science, Aberystwyth University, Gogerddan Campus. Aberystwyth, SY23 3EB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela F.","family":"Jones","sequence":"additional","affiliation":[{"name":"1 Leeds Institute of Molecular Medicine, Section of Experimental Therapeutics, 2Leeds Institute of Molecular Medicine, Section of Molecular Gastroenterology, St. James's University Hospital, University of Leeds. Leeds, LS9 7TF and 3Institute of Biological, Environmental and Rural Science, Aberystwyth University, Gogerddan Campus. Aberystwyth, SY23 3EB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narcis","family":"Fernandez-Fuentes","sequence":"additional","affiliation":[{"name":"1 Leeds Institute of Molecular Medicine, Section of Experimental Therapeutics, 2Leeds Institute of Molecular Medicine, Section of Molecular Gastroenterology, St. James's University Hospital, University of Leeds. Leeds, LS9 7TF and 3Institute of Biological, Environmental and Rural Science, Aberystwyth University, Gogerddan Campus. Aberystwyth, SY23 3EB, UK"},{"name":"1 Leeds Institute of Molecular Medicine, Section of Experimental Therapeutics, 2Leeds Institute of Molecular Medicine, Section of Molecular Gastroenterology, St. James's University Hospital, University of Leeds. Leeds, LS9 7TF and 3Institute of Biological, Environmental and Rural Science, Aberystwyth University, Gogerddan Campus. Aberystwyth, SY23 3EB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,5,4]]},"reference":[{"key":"2023012512432364200_B1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1006\/jmbi.2001.4857","article-title":"Structure-based analysis of protein-RNA interactions using the program ENTANGLE","volume":"311","author":"Allers","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2023012512432364200_B2","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":"2023012512432364200_B3","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1145\/235815.235821","article-title":"The Quickhull algorithm for convex hulls","volume":"22","author":"Barber","year":"1996","journal-title":"ACM Trans. Mathematical Softw."},{"key":"2023012512432364200_B4","first-page":"2611","article-title":"Structure Based Prediction of Binding Residues on DNA-binding Proteins","volume":"3","author":"Bhardwaj","year":"2005","journal-title":"Conf Proc IEEE Eng Med Biol Soc"},{"key":"2023012512432364200_B5","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1186\/1471-2105-10-379","article-title":"SitesIdentify: a protein functional site prediction tool","volume":"10","author":"Bray","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2023012512432364200_B6","volume-title":"Classification and Regression Trees.","author":"Breiman","year":"1984"},{"issue":"Suppl. 1","key":"2023012512432364200_B7","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1186\/1471-2105-9-S1-S13","article-title":"Functional site prediction selects correct protein models","volume":"9","author":"Chelliah","year":"2008","journal-title":"BMC Bioinformatics"},{"issue":"Suppl. 12","key":"2023012512432364200_B8","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1186\/1471-2105-9-S12-S6","article-title":"Predicting RNA-binding sites of proteins using support vector machines and evolutionary information","volume":"9","author":"Cheng","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"2023012512432364200_B9","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/prot.20842","article-title":"WHISCY: what information does surface conservation yield? Application to data-driven docking","volume":"63","author":"de Vries","year":"2006","journal-title":"Proteins"},{"key":"2023012512432364200_B10","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.bi.64.070195.003113","article-title":"Protein-RNA recognition","volume":"64","author":"Draper","year":"1995","journal-title":"Ann. Rev. Biochem."},{"key":"2023012512432364200_B11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/1097-0134(20010501)43:2<89::AID-PROT1021>3.0.CO;2-H","article-title":"Residue frequencies and pairing preferences at protein-protein interfaces","volume":"43","author":"Glaser","year":"2001","journal-title":"Proteins"},{"key":"2023012512432364200_B12","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0022-2836(02)00442-4","article-title":"Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations","volume":"320","author":"Guerois","year":"2002","journal-title":"J. Mol. Biol."},{"key":"2023012512432364200_B13","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1002\/prot.22830","article-title":"Protein-protein docking benchmark version 4.0","volume":"78","author":"Hwang","year":"2010","journal-title":"Proteins"},{"key":"2023012512432364200_B14","doi-asserted-by":"crossref","first-page":"W489","DOI":"10.1093\/nar\/gkm422","article-title":"siteFiNDER| 3D: a web-based tool for predicting the location of functional sites in proteins","volume":"35","author":"Innis","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2023012512432364200_B15","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1006\/jmbi.1999.2659","article-title":"Protein-DNA interactions: a structural analysis","volume":"287","author":"Jones","year":"1999","journal-title":"J. Mol. Biol."},{"key":"2023012512432364200_B16","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/nar\/29.4.943","article-title":"Protein-RNA interactions: a structural analysis","volume":"29","author":"Jones","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2023012512432364200_B17","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1006\/jmbi.2001.4540","article-title":"Three-dimensional cluster analysis identifies interfaces and functional residue clusters in proteins","volume":"307","author":"Landgraf","year":"2001","journal-title":"J. Mol. Biol."},{"key":"2023012512432364200_B18","first-page":"18","article-title":"Classification and Regression by random Forest","volume":"2","author":"Liaw","year":"2002","journal-title":"R News"},{"key":"2023012512432364200_B19","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1093\/bioinformatics\/btq253","article-title":"Prediction of protein-RNA binding sites by a random forest method with combined features","volume":"26","author":"Liu","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012512432364200_B20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.str.2009.11.012","article-title":"The structural basis of peptide-protein binding strategies","volume":"18","author":"London","year":"2010","journal-title":"Structure"},{"key":"2023012512432364200_B21","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2000-1-1-reviews001","article-title":"An overview of the structures of protein-DNA complexes","volume":"1","author":"Luscombe","year":"2000","journal-title":"Genome Biol."},{"key":"2023012512432364200_B22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1186\/1471-2105-10-341","article-title":"Exploiting structural and topological information to improve prediction of RNA-protein binding sites","volume":"10","author":"Maetschke","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2023012512432364200_B23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1472-6807-8-21","article-title":"PSAIA - protein structure and interaction analyzer","volume":"8","author":"Mihel","year":"2008","journal-title":"BMC Struct. Biol."},{"key":"2023012512432364200_B24","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/S0022-2836(05)80134-2","article-title":"SCOP: a structural classification of proteins database for the investigation of sequences and structures","volume":"247","author":"Murzin","year":"1995","journal-title":"J. Mol. Biol."},{"key":"2023012512432364200_B25","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1093\/bioinformatics\/17.8.700","article-title":"AL2CO: calculation of positional conservation in a protein sequence alignment","volume":"17","author":"Pei","year":"2001","journal-title":"Bioinformatics"},{"key":"2023012512432364200_B26","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.copbio.2008.06.004","article-title":"Peptide-mediated interactions in biological systems: new discoveries and applications","volume":"19","author":"Petsalaki","year":"2008","journal-title":"Curr. Opin. Biotechnol."},{"key":"2023012512432364200_B27","doi-asserted-by":"crossref","first-page":"e1000335","DOI":"10.1371\/journal.pcbi.1000335","article-title":"Accurate prediction of peptide binding sites on protein surfaces","volume":"5","author":"Petsalaki","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2023012512432364200_B28","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jmb.2007.03.036","article-title":"HotPatch: a statistical approach to finding biologically relevant features on protein surfaces","volume":"369","author":"Pettit","year":"2007","journal-title":"J. Mol. Biol."},{"key":"2023012512432364200_B29","doi-asserted-by":"crossref","first-page":"D61","DOI":"10.1093\/nar\/gkl842","article-title":"NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins","volume":"35","author":"Pruitt","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2023012512432364200_B30","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1186\/1471-2105-12-352","article-title":"Improving the prediction of protein binding sites by combining heterogeneous data and Voronoi diagrams","volume":"12","author":"Segura","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023012512432364200_B31","doi-asserted-by":"crossref","first-page":"e1000278","DOI":"10.1371\/journal.pcbi.1000278","article-title":"Prediction of protein-protein interaction sites in sequences and 3D structures by random forests","volume":"5","author":"Sikic","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2023012512432364200_B32","doi-asserted-by":"crossref","first-page":"W578","DOI":"10.1093\/nar\/gkm294","article-title":"RNABindR: a server for analyzing and predicting RNA-binding sites in proteins","volume":"35","author":"Terribilini","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2023012512432364200_B33","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1093\/nar\/gkm008","article-title":"DISPLAR: an accurate method for predicting DNA-binding sites on protein surfaces","volume":"35","author":"Tjong","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2023012512432364200_B34","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nature750","article-title":"Comparative assessment of large-scale data sets of protein-protein interactions","volume":"417","author":"von Mering","year":"2002","journal-title":"Nature"},{"key":"2023012512432364200_B35","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/protein\/8.2.127","article-title":"LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions","volume":"8","author":"Wallace","year":"1995","journal-title":"Protein Eng."},{"key":"2023012512432364200_B36","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/prot.22898","article-title":"An accurate feature-based method for identifying DNA-binding residues on protein surfaces","volume":"79","author":"Xiong","year":"2011","journal-title":"Proteins"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/14\/1845\/48870742\/bioinformatics_28_14_1845.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/14\/1845\/48870742\/bioinformatics_28_14_1845.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T16:50:23Z","timestamp":1674665423000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/14\/1845\/218519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,4]]},"references-count":36,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2012,7,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts269","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,7,15]]},"published":{"date-parts":[[2012,5,4]]}}}