{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:46:37Z","timestamp":1773387997391,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"Supplement_2","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil","doi-asserted-by":"crossref","award":["23038.004007\/2014-82"],"award-info":[{"award-number":["23038.004007\/2014-82"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil","doi-asserted-by":"crossref","award":["051\/2013"],"award-info":[{"award-number":["051\/2013"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012116","name":"European Bioinformatics Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012116","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The discovery of protein\u2013ligand-binding sites is a major step for elucidating protein function and for investigating new functional roles. Detecting protein\u2013ligand-binding sites experimentally is time-consuming and expensive. Thus, a variety of in silico methods to detect and predict binding sites was proposed as they can be scalable, fast and present low cost.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We proposed Graph-based Residue neighborhood Strategy to Predict binding sites (GRaSP), a novel residue centric and scalable method to predict ligand-binding site residues. It is based on a supervised learning strategy that models the residue environment as a graph at the atomic level. Results show that GRaSP made compatible or superior predictions when compared with methods described in the literature. GRaSP outperformed six other residue-centric methods, including the one considered as state-of-the-art. Also, our method achieved better results than the method from CAMEO independent assessment. GRaSP ranked second when compared with five state-of-the-art pocket-centric methods, which we consider a significant result, as it was not devised to predict pockets. Finally, our method proved scalable as it took 10\u201320\u2009s on average to predict the binding site for a protein complex whereas the state-of-the-art residue-centric method takes 2\u20135\u2009h on average.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The source code and datasets are available at https:\/\/github.com\/charles-abreu\/GRaSP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa805","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T19:13:50Z","timestamp":1599592430000},"page":"i726-i734","source":"Crossref","is-referenced-by-count":28,"title":["GRaSP: a graph-based residue neighborhood strategy to\u00a0predict binding sites"],"prefix":"10.1093","volume":"36","author":[{"given":"Charles A","family":"Santana","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology"},{"name":"Department of Computer Science, Universidade Federal de Minas Gerais , Belo Horizonte 31270-901, Brazil"}]},{"given":"Sabrina de A","family":"Silveira","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Universidade Federal de Vi\u00e7osa , Vi\u00e7osa 36570-900, Brazil"},{"name":"Institute of Technological Sciences (ICT), Advanced Campus at Itabira, Universidade Federal de Itajub\u00e1 , Itabira 35903-087, Brazil"}]},{"given":"Jo\u00e3o P A","family":"Moraes","sequence":"additional","affiliation":[{"name":"Institute of Technological Sciences (ICT), Advanced Campus at Itabira, Universidade Federal de Itajub\u00e1 , Itabira 35903-087, Brazil"}]},{"given":"Sandro C","family":"Izidoro","sequence":"additional","affiliation":[{"name":"Institute of Technological Sciences (ICT), Advanced Campus at Itabira, Universidade Federal de Itajub\u00e1 , Itabira 35903-087, Brazil"}]},{"given":"Raquel C","family":"de Melo-Minardi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology"},{"name":"Department of Computer Science, Universidade Federal de Minas Gerais , Belo Horizonte 31270-901, Brazil"}]},{"given":"Ant\u00f3nio J M","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus , Hinxton, Cambridge CB10 1SD, UK"}]},{"given":"Jonathan D","family":"Tyzack","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus , Hinxton, Cambridge CB10 1SD, UK"}]},{"given":"Neera","family":"Borkakoti","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus , Hinxton, Cambridge CB10 1SD, UK"}]},{"given":"Janet M","family":"Thornton","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus , Hinxton, Cambridge CB10 1SD, UK"}]}],"member":"286","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"2023062409324788400_btaa805-B1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1073\/pnas.0707684105","article-title":"A threading-based method (findsite) for ligand-binding site prediction and functional annotation","volume":"105","author":"Brylinski","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023062409324788400_btaa805-B2","doi-asserted-by":"crossref","first-page":"e1000585","DOI":"10.1371\/journal.pcbi.1000585","article-title":"Predicting protein ligand binding sites by combining evolutionary sequence conservation and 3D structure","volume":"5","author":"Capra","year":"2009","journal-title":"PLoS Comput. Biol"},{"key":"2023062409324788400_btaa805-B3","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.str.2011.02.015","article-title":"A critical comparative assessment of predictions of protein-binding sites for biologically relevant organic compounds","volume":"19","author":"Chen","year":"2011","journal-title":"Structure"},{"key":"2023062409324788400_btaa805-B4","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1093\/bioinformatics\/btp163","article-title":"Biopython: freely available python tools for computational molecular biology and bioinformatics","volume":"25","author":"Cock","year":"2009","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B5","doi-asserted-by":"crossref","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"Uniprot: a worldwide hub of protein knowledge","volume":"47","author":"Consortium","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B6","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1021\/acs.jcim.7b00307","article-title":"Identification of protein\u2013ligand binding sites by sequence information and ensemble classifier","volume":"57","author":"Ding","year":"2017","journal-title":"J. Chem. Inf. Model"},{"key":"2023062409324788400_btaa805-B7","doi-asserted-by":"crossref","first-page":"5722","DOI":"10.1021\/jacs.6b02682","article-title":"Interaction entropy: a new paradigm for highly efficient and reliable computation of protein\u2013ligand binding free energy","volume":"138","author":"Duan","year":"2016","journal-title":"J. Am. Chem. Soc"},{"key":"2023062409324788400_btaa805-B8","doi-asserted-by":"crossref","first-page":"D427","DOI":"10.1093\/nar\/gky995","article-title":"The pfam protein families database in 2019","volume":"47","author":"El-Gebali","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1186\/s12859-017-1789-3","article-title":"Vermont: a multi-perspective visual interactive platform for mutational analysis","volume":"18","author":"Fassio","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"2023062409324788400_btaa805-B10","author":"Fassio","year":"2019"},{"key":"2023062409324788400_btaa805-B11","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1093\/bioinformatics\/btu784","article-title":"LigDig: a web server for querying ligand\u2013protein interactions","volume":"31","author":"Fuller","year":"2015","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B12","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/prot.24495","article-title":"Assessment of ligand binding site predictions in casp10","volume":"82","author":"Gallo Cassarino","year":"2014","journal-title":"Proteins Struct. Funct. Bioinf"},{"key":"2023062409324788400_btaa805-B13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10994-006-6226-1","article-title":"Extremely randomized trees","volume":"63","author":"Geurts","year":"2006","journal-title":"Mach. Learn"},{"key":"2023062409324788400_btaa805-B14","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1093\/bioinformatics\/btp562","article-title":"EasyMIFS and SiteHound: a toolkit for the identification of ligand-binding sites in protein structures","volume":"25","author":"Ghersi","year":"2009","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B15","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/prot.25431","article-title":"Continuous automated model evaluation (CAMEO) complementing the critical assessment of structure prediction in casp12","volume":"86","author":"Haas","year":"2018","journal-title":"Proteins Struct. Funct. Bioinf"},{"key":"2023062409324788400_btaa805-B16","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1021\/jm061277y","article-title":"Diverse, high-quality test set for the validation of protein\u2013ligand docking performance","volume":"50","author":"Hartshorn","year":"2007","journal-title":"J. Med. Chem"},{"key":"2023062409324788400_btaa805-B17","doi-asserted-by":"crossref","first-page":"W413","DOI":"10.1093\/nar\/gkp281","article-title":"SiteHound-web: a server for ligand binding site identification in protein structures","volume":"37","author":"Hernandez","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B18","author":"Hubbard","year":"1993"},{"key":"2023062409324788400_btaa805-B19","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1093\/bioinformatics\/btu746","article-title":"GASS: identifying enzyme active sites with genetic algorithms","volume":"31","author":"Izidoro","year":"2015","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B20","doi-asserted-by":"crossref","first-page":"W345","DOI":"10.1093\/nar\/gkz424","article-title":"PrankWeb: a web server for ligand binding site prediction and visualization","volume":"47","author":"Jendele","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B21","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1093\/bioinformatics\/btx350","article-title":"Deepsite: protein-binding site predictor using 3D-convolutional neural networks","volume":"33","author":"Jim\u00e9nez","year":"2017","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B22","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1093\/bioinformatics\/btv593","article-title":"Automatic generation of bioinformatics tools for predicting protein\u2013ligand binding sites","volume":"32","author":"Komiyama","year":"2016","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13321-018-0285-8","article-title":"P2rank: machine learning based tool for rapid and accurate prediction of ligand binding sites from protein structure","volume":"10","author":"Kriv\u00e1k","year":"2018","journal-title":"J. Cheminf"},{"key":"2023062409324788400_btaa805-B24","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/1471-2105-10-168","article-title":"Fpocket: an open source platform for ligand pocket detection","volume":"10","author":"Le Guilloux","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2023062409324788400_btaa805-B26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41401-019-0228-6","article-title":"CB-Dock: a web server for cavity detection-guided protein\u2013ligand blind docking","volume":"41","author":"Liu","year":"2020","journal-title":"Acta Pharmacol. Sin"},{"key":"2023062409324788400_btaa805-B27","doi-asserted-by":"crossref","first-page":"D219","DOI":"10.1093\/nar\/gkl897","article-title":"FireDB\u2014a database of functionally important residues from proteins of known structure","volume":"35","author":"Lopez","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B28","doi-asserted-by":"crossref","first-page":"W573","DOI":"10.1093\/nar\/gkm297","article-title":"firestar\u2014prediction of functionally important residues using structural templates and alignment reliability","volume":"35","author":"L\u00f3pez","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B29","doi-asserted-by":"crossref","first-page":"W235","DOI":"10.1093\/nar\/gkr437","article-title":"firestar\u2014advances in the prediction of functionally important residues","volume":"39","author":"Lopez","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B30","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s10822-019-00235-7","article-title":"Computational methods and tools for binding site recognition between proteins and small molecules: from classical geometrical approaches to modern machine learning strategies","volume":"33","author":"Macari","year":"2019","journal-title":"J. Comput. Aided Mol. Des"},{"key":"2023062409324788400_btaa805-B31","doi-asserted-by":"crossref","first-page":"W315","DOI":"10.1093\/nar\/gkx337","article-title":"GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms","volume":"45","author":"Moraes","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.sbi.2017.09.001","article-title":"NMR studies of ligand binding","volume":"48","author":"Nitsche","year":"2018","journal-title":"Curr. Opin. Struct. Biol"},{"key":"2023062409324788400_btaa805-B33","first-page":"2825","article-title":"Scikit-learn: machine learning in python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res"},{"key":"2023062409324788400_btaa805-B34","doi-asserted-by":"crossref","first-page":"129D","DOI":"10.1093\/nar\/gkh028","article-title":"The catalytic site atlas: a resource of catalytic sites and residues identified in enzymes using structural data","volume":"32","author":"Porter","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B35","doi-asserted-by":"crossref","first-page":"29829","DOI":"10.3390\/ijms161226202","article-title":"Proteins and their interacting partners: an introduction to protein\u2013ligand binding site prediction methods","volume":"16","author":"Roche","year":"2015","journal-title":"Int. J. Mol. Sci"},{"key":"2023062409324788400_btaa805-B36","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1093\/bioinformatics\/btq543","article-title":"The binding site distance test score: a robust method for the assessment of predicted protein binding sites","volume":"26","author":"Roche","year":"2010","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B37","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/1471-2105-12-160","article-title":"FunFOLD: an improved automated method for the prediction of ligand binding residues using 3D models of proteins","volume":"12","author":"Roche","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023062409324788400_btaa805-B38","doi-asserted-by":"crossref","first-page":"W303","DOI":"10.1093\/nar\/gkt498","article-title":"The FunFOLD2 server for the prediction of protein\u2013ligand interactions","volume":"41","author":"Roche","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B39","doi-asserted-by":"crossref","first-page":"W471","DOI":"10.1093\/nar\/gks372","article-title":"Cofactor: an accurate comparative algorithm for structure-based protein function annotation","volume":"40","author":"Roy","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B40","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/prot.23174","article-title":"Assessment of ligand-binding residue predictions in casp9","volume":"79","author":"Schmidt","year":"2011","journal-title":"Proteins Struct. Funct. Bioinf"},{"key":"2023062409324788400_btaa805-B41","doi-asserted-by":"crossref","first-page":"W582","DOI":"10.1093\/nar\/gkq383","article-title":"Fpocket: online tools for protein ensemble pocket detection and tracking","volume":"38","author":"Schmidtke","year":"2010","journal-title":"Nucleic Acids Research"},{"key":"2023062409324788400_btaa805-B42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/3068335","article-title":"DBSCAN revisited, revisited: why and how you should (still) use DBSCAN","volume":"42","author":"Schubert","year":"2017","journal-title":"ACM Trans. Database Syst. (TODS)"},{"key":"2023062409324788400_btaa805-B43","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/j.str.2013.08.007","article-title":"Protein modeling: what happened to the protein structure gap?","volume":"21","author":"Schwede","year":"2013","journal-title":"Structure"},{"key":"2023062409324788400_btaa805-B44","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1016\/j.drudis.2017.08.004","article-title":"Structural coverage of the proteome for pharmaceutical applications","volume":"22","author":"Somody","year":"2017","journal-title":"Drug Discov. Today"},{"key":"2023062409324788400_btaa805-B45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbpa.2018.05.003","article-title":"Cryptic binding sites on proteins: definition, detection, and druggability","volume":"44","author":"Vajda","year":"2018","journal-title":"Curr. Opin. Chem. Biol"},{"key":"2023062409324788400_btaa805-B46","doi-asserted-by":"crossref","first-page":"180901","DOI":"10.1063\/1.4947037","article-title":"Perspective: defining and quantifying the role of dynamics in enzyme catalysis","volume":"144","author":"Warshel","year":"2016","journal-title":"J. Chem. Phys"},{"key":"2023062409324788400_btaa805-B47","doi-asserted-by":"crossref","first-page":"W438","DOI":"10.1093\/nar\/gky439","article-title":"COACH-D: improved protein\u2013ligand binding sites prediction with refined ligand-binding poses through molecular docking","volume":"46","author":"Wu","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B48","doi-asserted-by":"crossref","first-page":"D1096","DOI":"10.1093\/nar\/gks966","article-title":"BioLiP: a semi-manually curated database for biologically relevant ligand\u2013protein interactions","volume":"41","author":"Yang","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023062409324788400_btaa805-B49","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1093\/bioinformatics\/btt447","article-title":"Protein\u2013ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment","volume":"29","author":"Yang","year":"2013","journal-title":"Bioinformatics"},{"key":"2023062409324788400_btaa805-B50","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1093\/bioinformatics\/btr331","article-title":"Identification of cavities on protein surface using multiple computational approaches for drug binding site prediction","volume":"27","author":"Zhang","year":"2011","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/Supplement_2\/i726\/50693483\/btaa805.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/36\/Supplement_2\/i726\/50693483\/btaa805.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T23:55:16Z","timestamp":1687650916000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/36\/Supplement_2\/i726\/6055937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":49,"journal-issue":{"issue":"Supplement_2","published-print":{"date-parts":[[2020,12,30]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa805","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,12]]},"published":{"date-parts":[[2020,12]]}}}