{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:06:33Z","timestamp":1777485993502,"version":"3.51.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"S4","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The identification of ligand binding sites is a key task in the annotation of proteins with known structure but uncharacterized function. Here we describe a knowledge-based method exploiting the observation that unrelated binding sites share small structural motifs that bind the same chemical fragments irrespective of the nature of the ligand as a whole.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>PDBinder compares a query protein against a library of binding and non-binding protein surface regions derived from the PDB. The results of the comparison are used to derive a propensity value for each residue which is correlated with the likelihood that the residue is part of a ligand binding site. The method was applied to two different problems: i) the prediction of ligand binding residues and ii) the identification of which surface cleft harbours the binding site. In both cases PDBinder performed consistently better than existing methods.<\/jats:p>\n            <jats:p>PDBinder has been trained on a non-redundant set of 1356 high-quality protein-ligand complexes and tested on a set of 239 holo and apo complex pairs. We obtained an MCC of 0.313 on the holo set with a PPV of 0.413 while on the apo set we achieved an MCC of 0.271 and a PPV of 0.372.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We show that PDBinder performs better than existing methods. The good performance on the unbound proteins is extremely important for real-world applications where the location of the binding site is unknown. Moreover, since our approach is orthogonal to those used in other programs, the PDBinder propensity value can be integrated in other algorithms further increasing the final performance.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-13-s4-s17","type":"journal-article","created":{"date-parts":[[2012,5,29]],"date-time":"2012-05-29T17:25:27Z","timestamp":1338312327000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Identification of binding pockets in protein structures using a knowledge-based potential derived from local structural similarities"],"prefix":"10.1186","volume":"13","author":[{"given":"Valerio","family":"Bianchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Federico","family":"Gherardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Helmer-Citterich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Ausiello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,3,28]]},"reference":[{"key":"5114_CR1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1093\/bfgp\/eln030","volume":"7","author":"PF Gherardini","year":"2008","unstructured":"Gherardini PF, Helmer-Citterich M: Structure-based function prediction: approaches and applications. Brief Funct Genomic Proteomic 2008, 7: 291\u2013302. 10.1093\/bfgp\/eln030","journal-title":"Brief Funct Genomic Proteomic"},{"key":"5114_CR2","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/0263-7855(95)00073-9","volume":"13","author":"RA Laskowski","year":"1995","unstructured":"Laskowski RA: SURFNET: a program for visualizing molecular surfaces, cavities, and intermolecular interactions. J Mol Graph 1995, 13: 323\u2013330. 307\u2013308 307-308 10.1016\/0263-7855(95)00073-9","journal-title":"J Mol Graph"},{"key":"5114_CR3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1472-6807-6-19","volume":"6","author":"B Huang","year":"2006","unstructured":"Huang B, Schroeder M: LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree of conservation. BMC Struct Biol 2006, 6: 19. 10.1186\/1472-6807-6-19","journal-title":"BMC Struct Biol"},{"key":"5114_CR4","doi-asserted-by":"publisher","first-page":"e1000585","DOI":"10.1371\/journal.pcbi.1000585","volume":"5","author":"JA Capra","year":"2009","unstructured":"Capra JA, Laskowski RA, Thornton JM, Singh M, Funkhouser TA: Predicting protein ligand binding sites by combining evolutionary sequence conservation and 3D structure. PLoS Comput Biol 2009, 5: e1000585. 10.1371\/journal.pcbi.1000585","journal-title":"PLoS Comput Biol"},{"key":"5114_CR5","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1006\/jmbi.1996.0077","volume":"256","author":"KP Peters","year":"1996","unstructured":"Peters KP, Fauck J, Fr\u00f6mmel C: The automatic search for ligand binding sites in proteins of known three-dimensional structure using only geometric criteria. J Mol Biol 1996, 256: 201\u2013213. 10.1006\/jmbi.1996.0077","journal-title":"J Mol Biol"},{"issue":"Suppl 2","key":"5114_CR6","doi-asserted-by":"publisher","first-page":"W242","DOI":"10.1093\/nar\/gkr356","volume":"39","author":"KP Tan","year":"2011","unstructured":"Tan KP, Varadarajan R, Madhusudhan MS: DEPTH: a web server to compute depth and predict small-molecule binding cavities in proteins. Nucleic Acids Res 2011,39(Suppl 2):W242\u2013248.","journal-title":"Nucleic Acids Res"},{"key":"5114_CR7","first-page":"2438","volume":"5","author":"RA Laskowski","year":"1996","unstructured":"Laskowski RA, Luscombe NM, Swindells MB, Thornton JM: Protein clefts in molecular recognition and function. Protein Sci 1996, 5: 2438\u20132452.","journal-title":"Protein Sci"},{"key":"5114_CR8","doi-asserted-by":"publisher","first-page":"D667","DOI":"10.1093\/nar\/gkm839","volume":"36","author":"BH Dessailly","year":"2008","unstructured":"Dessailly BH, Lensink MF, Orengo CA, Wodak SJ: LigASite--a database of biologically relevant binding sites in proteins with known apo-structures. Nucleic Acids Res 2008, 36: D667-D673.","journal-title":"Nucleic Acids Res"},{"key":"5114_CR9","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1002\/prot.22067","volume":"73","author":"M Morita","year":"2008","unstructured":"Morita M, Nakamura S, Shimizu K: Highly accurate method for ligand-binding site prediction in unbound state (apo) protein structures. Proteins 2008, 73: 468\u2013479. 10.1002\/prot.22067","journal-title":"Proteins"},{"key":"5114_CR10","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1093\/bioinformatics\/bti315","volume":"21","author":"ATR Laurie","year":"2005","unstructured":"Laurie ATR, Jackson RM: Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites. Bioinformatics 2005, 21: 1908\u20131916. 10.1093\/bioinformatics\/bti315","journal-title":"Bioinformatics"},{"key":"5114_CR11","doi-asserted-by":"publisher","first-page":"W413","DOI":"10.1093\/nar\/gkp281","volume":"37","author":"M Hernandez","year":"2009","unstructured":"Hernandez M, Ghersi D, Sanchez R: SITEHOUND-web: a server for ligand binding site identification in protein structures. Nucleic Acids Res 2009, 37: W413-W416. 10.1093\/nar\/gkp281","journal-title":"Nucleic Acids Res"},{"key":"5114_CR12","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/j.jmb.2004.10.055","volume":"344","author":"G Amitai","year":"2004","unstructured":"Amitai G, Shemesh A, Sitbon E, et al.: Network analysis of protein structures identifies functional residues. J Mol Biol 2004, 344: 1135\u20131146. 10.1016\/j.jmb.2004.10.055","journal-title":"J Mol Biol"},{"key":"5114_CR13","doi-asserted-by":"publisher","first-page":"12473","DOI":"10.1073\/pnas.211436698","volume":"98","author":"MJ Ondrechen","year":"2001","unstructured":"Ondrechen MJ, Clifton JG, Ringe D: THEMATICS: a simple computational predictor of enzyme function from structure. Proc Natl Acad Sci USA 2001, 98: 12473\u201312478. 10.1073\/pnas.211436698","journal-title":"Proc Natl Acad Sci USA"},{"key":"5114_CR14","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/S0022-2836(03)00207-9","volume":"327","author":"M Ota","year":"2003","unstructured":"Ota M, Kinoshita K, Nishikawa K: Prediction of catalytic residues in enzymes based on known tertiary structure, stability profile, and sequence conservation. J Mol Biol 2003, 327: 1053\u20131064. 10.1016\/S0022-2836(03)00207-9","journal-title":"J Mol Biol"},{"key":"5114_CR15","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.1093\/bioinformatics\/btq490","volume":"26","author":"W Mehio","year":"2010","unstructured":"Mehio W, Kemp GJL, Taylor P, Walkinshaw MD: Identification of protein binding surfaces using surface triplet propensities. Bioinformatics 2010, 26: 2549\u20132555. 10.1093\/bioinformatics\/btq490","journal-title":"Bioinformatics"},{"key":"5114_CR16","doi-asserted-by":"crossref","unstructured":"Wass MN, Kelley LA, Sternberg MJE: 3DLigandSite: predicting ligand-binding sites using similar structures. Nucleic Acids Res 2010, (38 Web Server):W469-W473.","DOI":"10.1093\/nar\/gkq406"},{"key":"5114_CR17","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1073\/pnas.0707684105","volume":"105","author":"M Brylinski","year":"2008","unstructured":"Brylinski M, Skolnick J: A threading-based method (FINDSITE) for ligand-binding site prediction and functional annotation. Proc Natl Acad Sci USA 2008, 105: 129\u2013134. 10.1073\/pnas.0707684105","journal-title":"Proc Natl Acad Sci USA"},{"key":"5114_CR18","doi-asserted-by":"crossref","unstructured":"Lopez G, Valencia A, Tress ML: firestar--prediction of functionally important residues using structural templates and alignment reliability. Nucleic Acids Res 2007, (35 Web Server):W573-W577.","DOI":"10.1093\/nar\/gkm297"},{"key":"5114_CR19","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1093\/bioinformatics\/btq232","volume":"26","author":"K Kasahara","year":"2010","unstructured":"Kasahara K, Kinoshita K, Takagi T: Ligand-binding site prediction of proteins based on known fragment-fragment interactions. Bioinformatics 2010, 26: 1493\u20131499. 10.1093\/bioinformatics\/btq232","journal-title":"Bioinformatics"},{"key":"5114_CR20","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1002\/prot.21487","volume":"69","author":"V Ramensky","year":"2007","unstructured":"Ramensky V, Sobol A, Zaitseva N, Rubinov A, Zosimov V: A novel approach to local similarity of protein binding sites substantially improves computational drug design results. Proteins 2007, 69: 349\u2013357. 10.1002\/prot.21487","journal-title":"Proteins"},{"key":"5114_CR21","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1006\/jmbi.1999.2809","volume":"289","author":"ML Verdonk","year":"1999","unstructured":"Verdonk ML, Cole JC, Taylor R: SuperStar: a knowledge-based approach for identifying interaction sites in proteins. J Mol Biol 1999, 289: 1093\u20131108. 10.1006\/jmbi.1999.2809","journal-title":"J Mol Biol"},{"key":"5114_CR22","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/1471-2105-10-182","volume":"10","author":"G Ausiello","year":"2009","unstructured":"Ausiello G, Gherardini PF, Gatti E, Incani O, Helmer-Citterich M: Structural motifs recurring in different folds recognize the same ligand fragments. BMC Bioinformatics 2009, 10: 182. 10.1186\/1471-2105-10-182","journal-title":"BMC Bioinformatics"},{"key":"5114_CR23","doi-asserted-by":"publisher","first-page":"3809","DOI":"10.1093\/nar\/gkq090","volume":"38","author":"PF Gherardini","year":"2010","unstructured":"Gherardini PF, Ausiello G, Russell RB, Helmer-Citterich M: Modular architecture of nucleotide-binding pockets. Nucleic Acids Res 2010, 38: 3809\u20133816. 10.1093\/nar\/gkq090","journal-title":"Nucleic Acids Res"},{"issue":"Suppl 4","key":"5114_CR24","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1186\/1471-2105-6-S4-S5","volume":"6","author":"G Ausiello","year":"2005","unstructured":"Ausiello G, Via A, Helmer-Citterich M: Query3d: a new method for high-throughput analysis of functional residues in protein structures. BMC Bioinformatics 2005,6(Suppl 4):S5. 10.1186\/1471-2105-6-S4-S5","journal-title":"BMC Bioinformatics"},{"key":"5114_CR25","doi-asserted-by":"publisher","first-page":"e11988","DOI":"10.1371\/journal.pone.0011988","volume":"5","author":"PF Gherardini","year":"2010","unstructured":"Gherardini PF, Ausiello G, Helmer-Citterich M: Superpose3D: a local structural comparison program that allows for user-defined structure representations. PloS One 2010, 5: e11988. 10.1371\/journal.pone.0011988","journal-title":"PloS One"},{"key":"5114_CR26","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/0014-5793(94)00648-2","volume":"349","author":"HO Villar","year":"1994","unstructured":"Villar HO, Kauvar LM: Amino acid preferences at protein binding sites. FEBS Lett 1994, 349: 125\u2013130. 10.1016\/0014-5793(94)00648-2","journal-title":"FEBS Lett"},{"key":"5114_CR27","unstructured":"Q-SiteFinder Webserver[http:\/\/www.modelling.leeds.ac.uk\/qsitefinder\/]"},{"key":"5114_CR28","unstructured":"Blastclust Sequence Clusters[ftp:\/\/resources.rcsb.org\/sequence\/clusters\/]"},{"key":"5114_CR29","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/j.jmb.2005.11.044","volume":"355","author":"ND Gold","year":"2006","unstructured":"Gold ND, Jackson RM: Fold independent structural comparisons of protein-ligand binding sites for exploring functional relationships. J Mol Biol 2006, 355: 1112\u20131124. 10.1016\/j.jmb.2005.11.044","journal-title":"J Mol Biol"},{"key":"5114_CR30","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/protein\/6.1.29","volume":"6","author":"DS Gregory","year":"1993","unstructured":"Gregory DS, Martin AC, Cheetham JC, Rees AR: The prediction and characterization of metal binding sites in proteins. Protein Eng 1993, 6: 29\u201335. 10.1093\/protein\/6.1.29","journal-title":"Protein Eng"},{"key":"5114_CR31","doi-asserted-by":"crossref","unstructured":"Ausiello G, Zanzoni A, Peluso D, Via A, Helmer-Citterich M: pdbFun: mass selection and fast comparison of annotated PDB residues. Nucleic Acids Res 2005, (33 Web Server):W133-W137.","DOI":"10.1093\/nar\/gki499"},{"key":"5114_CR32","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/S0968-0004(98)01253-5","volume":"23","author":"K Henrick","year":"1998","unstructured":"Henrick K, Thornton JM: PQS: a protein quaternary structure file server. Trends Biochem Sci 1998, 23: 358. 10.1016\/S0968-0004(98)01253-5","journal-title":"Trends Biochem Sci"},{"key":"5114_CR33","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1093\/bioinformatics\/btg224","volume":"19","author":"G Wang","year":"2003","unstructured":"Wang G, Dunbrack RL: PISCES: a protein sequence culling server. Bioinformatics 2003, 19: 1589\u20131591. 10.1093\/bioinformatics\/btg224","journal-title":"Bioinformatics"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-13-S4-S17.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T18:36:49Z","timestamp":1630521409000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-13-S4-S17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,28]]},"references-count":33,"journal-issue":{"issue":"S4","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["5114"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-13-s4-s17","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,28]]},"assertion":[{"value":"28 March 2012","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"S17"}}