{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:17:18Z","timestamp":1763140638315},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T00:00:00Z","timestamp":1375056000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cheminform"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Many Protein Data Bank (PDB) users assume that the deposited structural models are of high quality but forget that these models are derived from the interpretation of experimental data. The accuracy of atom coordinates is not homogeneous between models or throughout the same model. To avoid basing a research project on a flawed model, we present a tool for assessing the quality of ligands and binding sites in crystallographic models from the PDB.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The Validation HElper for LIgands and Binding Sites (VHELIBS) is software that aims to ease the validation of binding site and ligand coordinates for non-crystallographers (i.e., users with little or no crystallography knowledge). Using a convenient graphical user interface, it allows one to check how ligand and binding site coordinates fit to the electron density map. VHELIBS can use models from either the PDB or the PDB_REDO databank of re-refined and re-built crystallographic models. The user can specify threshold values for a series of properties related to the fit of coordinates to electron density (Real Space R, Real Space Correlation Coefficient and average occupancy are used by default). VHELIBS will automatically classify residues and ligands as <jats:italic>Good<\/jats:italic>, <jats:italic>Dubious<\/jats:italic> or <jats:italic>Bad<\/jats:italic> based on the specified limits. The user is also able to visually check the quality of the fit of residues and ligands to the electron density map and reclassify them if needed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>VHELIBS allows inexperienced users to examine the binding site and the ligand coordinates in relation to the experimental data. This is an important step to evaluate models for their fitness for drug discovery purposes such as structure-based pharmacophore development and protein-ligand docking experiments.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1758-2946-5-36","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T12:14:23Z","timestamp":1375100063000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The good, the bad and the dubious: VHELIBS, a validation helper for ligands and binding sites"],"prefix":"10.1186","volume":"5","author":[{"given":"Adri\u00e0","family":"Cereto-Massagu\u00e9","sequence":"first","affiliation":[]},{"given":"Mar\u00eda Jos\u00e9","family":"Ojeda","sequence":"additional","affiliation":[]},{"given":"Robbie P","family":"Joosten","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Valls","sequence":"additional","affiliation":[]},{"given":"Miquel","family":"Mulero","sequence":"additional","affiliation":[]},{"given":"M Josepa","family":"Salvado","sequence":"additional","affiliation":[]},{"given":"Anna","family":"Arola-Arnal","sequence":"additional","affiliation":[]},{"given":"Llu\u00eds","family":"Arola","sequence":"additional","affiliation":[]},{"given":"Santiago","family":"Garcia-Vallv\u00e9","sequence":"additional","affiliation":[]},{"given":"Gerard","family":"Pujadas","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,7,29]]},"reference":[{"key":"476_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1126\/science.181.4096.223","volume":"181","author":"CB Anfinsen","year":"1973","unstructured":"Anfinsen CB: Principles that govern the folding of protein chains. Science (New York, NY). 1973, 181: 223-230. 10.1126\/science.181.4096.223.","journal-title":"Science (New York, NY)"},{"key":"476_CR2","doi-asserted-by":"publisher","first-page":"1868","DOI":"10.1126\/science.1113801","volume":"309","author":"P Bradley","year":"2005","unstructured":"Bradley P, Misura KMS, Baker D: Toward high-resolution de novo structure prediction for small proteins. Science (New York, NY). 2005, 309: 1868-1871. 10.1126\/science.1113801.","journal-title":"Science (New York, NY)"},{"key":"476_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/B978-012587073-3\/50003-9","volume-title":"Crystallography Made Crystal Clear: A Guide for Users of Macromolecular Models","author":"G Rhodes","year":"2006","unstructured":"Rhodes G, Cooper J: Model and molecule. Crystallography Made Crystal Clear: A Guide for Users of Macromolecular Models. 2006, Academic, 1-5."},{"key":"476_CR4","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1038\/nsb1203-980","volume":"10","author":"H Berman","year":"2003","unstructured":"Berman H, Henrick K, Nakamura H: Announcing the worldwide protein data bank. Nat Struct Biol. 2003, 10: 980-10.1038\/nsb1203-980.","journal-title":"Nat Struct Biol"},{"key":"476_CR5","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1107\/S0907444913000255","volume":"69","author":"Z Dauter","year":"2013","unstructured":"Dauter Z, Weiss MS, Einspahr H, Baker EN: Expectation bias and information content. Acta Crystallogr Sect D Struct Biol Cryst. 2013, 69: 141-141.","journal-title":"Acta Crystallogr Sect D Struct Biol Cryst"},{"key":"476_CR6","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/343687a0","volume":"343","author":"C-I Br\u00e4nd\u2019en","year":"1990","unstructured":"Br\u00e4nd\u2019en C-I, Alwyn Jones T: Between objectivity and subjectivity. Nature. 1990, 343: 687-689. 10.1038\/343687a0.","journal-title":"Nature"},{"key":"476_CR7","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1107\/S0108767390010224","volume":"47","author":"TA Jones","year":"1991","unstructured":"Jones TA, Zou JY, Cowan SW, Kjeldgaard M: Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr Sect A Found Cryst. 1991, 47: 110-119. 10.1107\/S0108767390010224.","journal-title":"Acta Crystallogr Sect A Found Cryst"},{"key":"476_CR8","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/j.str.2011.08.006","volume":"19","author":"RJ Read","year":"2011","unstructured":"Read RJ, Adams PD, Arendall WB, Brunger AT, Emsley P, Joosten RP, Kleywegt GJ, Krissinel EB, L\u00fctteke T, Otwinowski Z, Perrakis A, Richardson JS, Sheffler WH, Smith JL, Tickle IJ, Vriend G, Zwart PH: A new generation of crystallographic validation tools for the protein data bank. Structure (London, England: 1993). 2011, 19: 1395-1412. 10.1016\/j.str.2011.08.006.","journal-title":"Structure (London, England: 1993)"},{"key":"476_CR9","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1107\/S0907444911050359","volume":"68","author":"S Gore","year":"2012","unstructured":"Gore S, Velankar S, Kleywegt GJ: Implementing an x-ray validation pipeline for the protein data bank. Acta Crystallogr Sect D Biol Cryst. 2012, 68: 478-483. 10.1107\/S0907444911050359.","journal-title":"Acta Crystallogr Sect D Biol Cryst"},{"key":"476_CR10","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1002\/bip.22108","volume":"99","author":"JS Richardson","year":"2013","unstructured":"Richardson JS, Richardson DC: Studying and polishing the PDB\u2019s macromolecules. Biopolymers. 2013, 99: 170-182. 10.1002\/bip.22108.","journal-title":"Biopolymers"},{"key":"476_CR11","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1107\/S0907444912044423","volume":"69","author":"E Pozharski","year":"2013","unstructured":"Pozharski E, Weichenberger CX, Rupp B: Techniques, tools and best practices for ligand electron-density analysis and results from their application to deposited crystal structures. Acta Crystallogr Sect D Biol Cryst. 2013, 69: 150-67.","journal-title":"Acta Crystallogr Sect D Biol Cryst"},{"key":"476_CR12","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1107\/S1744309112044387","volume":"69","author":"CX Weichenberger","year":"2013","unstructured":"Weichenberger CX, Pozharski E, Rupp B: Visualizing ligand molecules in twilight electron density. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013, 69: 195-200.","journal-title":"Acta Crystallogr Sect F Struct Biol Cryst Commun"},{"key":"476_CR13","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman HM: The protein data bank. Nucleic Acids Res. 2000, 28: 235-242. 10.1093\/nar\/28.1.235.","journal-title":"Nucleic Acids Res"},{"key":"476_CR14","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1126\/science.317.5835.195","volume":"317","author":"RP Joosten","year":"2007","unstructured":"Joosten RP, Vriend G: PDB improvement starts with data deposition. Science (New York, NY). 2007, 317: 195-196. 10.1126\/science.317.5835.195.","journal-title":"Science (New York, NY)"},{"key":"476_CR15","doi-asserted-by":"publisher","first-page":"3392","DOI":"10.1093\/bioinformatics\/btr590","volume":"27","author":"RP Joosten","year":"2011","unstructured":"Joosten RP, Joosten K, Cohen SX, Vriend G, Perrakis A: Automatic rebuilding and optimization of crystallographic structures in the protein data bank. Bioinformatics (Oxford, England). 2011, 27: 3392-3398. 10.1093\/bioinformatics\/btr590.","journal-title":"Bioinformatics (Oxford, England)"},{"key":"476_CR16","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1107\/S0907444911054515","volume":"68","author":"RP Joosten","year":"2012","unstructured":"Joosten RP, Joosten K, Murshudov GN, Perrakis A: PDB_REDO: constructive validation, more than just looking for errors. Acta Crystallographica Section D. 2012, 68: 484-496. 10.1107\/S0108767312019034.","journal-title":"Acta Crystallographica Section D"},{"key":"476_CR17","unstructured":"The Jython Project. http:\/\/www.jython.org\/,"},{"key":"476_CR18","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1107\/S0021889810030256","volume":"43","author":"RM Hanson","year":"2010","unstructured":"Hanson RM: Jmol \u2013 a paradigm shift in crystallographic visualization. J Appl Cryst. 2010, 43: 1250-1260. 10.1107\/S0021889810030256.","journal-title":"J Appl Cryst"},{"key":"476_CR19","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1107\/S0907444904013253","volume":"60","author":"GJ Kleywegt","year":"2004","unstructured":"Kleywegt GJ, Harris MR, Zou JY, Taylor TC, W\u00e4hlby A, Jones TA: The Uppsala electron-density server. Acta Crystallogr Sect D Biol Cryst. 2004, 60: 2240-2249. 10.1107\/S0907444904013253.","journal-title":"Acta Crystallogr Sect D Biol Cryst"},{"key":"476_CR20","unstructured":"EDS - Uppsala Electron Density Server. http:\/\/eds.bmc.uu.se\/eds\/,"},{"key":"476_CR21","first-page":"bar009","volume":"2011","author":"M Magrane","year":"2011","unstructured":"Magrane M: UniProt Knowledgebase: a hub of integrated protein data. Database J Biol Databases Curat. 2011, 2011: bar009-","journal-title":"Database J Biol Databases Curat"},{"key":"476_CR22","doi-asserted-by":"publisher","first-page":"D1096","DOI":"10.1093\/nar\/gks966","volume":"41","author":"J Yang","year":"2013","unstructured":"Yang J, Roy A, Zhang Y: BioLiP: a semi-manually curated database for biologically relevant ligand-protein interactions. Nucleic Acids Res. 2013, 41: D1096-103. 10.1093\/nar\/gks966.","journal-title":"Nucleic Acids Res"},{"key":"476_CR23","doi-asserted-by":"publisher","first-page":"3614","DOI":"10.1021\/jm060015t","volume":"49","author":"SD Edmondson","year":"2006","unstructured":"Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park Y-J, Beconi M, Di Salvo J, Eiermann GJ, He H, Leiting B, Leone JF, Levorse DA, Lyons K, Patel RA, Patel SB, Petrov A, Scapin G, Shang J, Roy RS, Smith A, Wu JK, Xu S, Zhu B, Thornberry NA, Weber AE: (2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N, N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2006, 49: 3614-27. 10.1021\/jm060015t.","journal-title":"J Med Chem"},{"key":"476_CR24","unstructured":"RCSB Protein Data Bank - RCSB PDB - 3Q8W Structure Summary. http:\/\/www.rcsb.org\/pdb\/explore\/explore.do?structureId=3Q8W,"},{"key":"476_CR25","unstructured":"VHELIBS Online Documentation. https:\/\/github.com\/URVnutrigenomica-CTNS\/VHELIBS\/wiki,"},{"key":"476_CR26","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1107\/S0907444995014983","volume":"52","author":"GJ Kleywegt","year":"1996","unstructured":"Kleywegt GJ, Jones TA: xdlMAPMAN and xdlDATAMAN - programs for reformatting, analysis and manipulation of biomacromolecular electron-density maps and reflection data sets. Acta Crystallogr Sect D Biol Cryst. 1996, 52: 826-828. 10.1107\/S0907444995014983.","journal-title":"Acta Crystallogr Sect D Biol Cryst"},{"key":"476_CR27","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1107\/S0907444911035918","volume":"68","author":"IJ Tickle","year":"2012","unstructured":"Tickle IJ: Statistical quality indicators for electron-density maps. Acta Crystallogr Sect D Biol Cryst. 2012, 68: 454-467. 10.1107\/S0907444911035918.","journal-title":"Acta Crystallogr Sect D Biol Cryst"},{"key":"476_CR28","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/j.drudis.2012.06.011","volume":"17","author":"GL Warren","year":"2012","unstructured":"Warren GL, Do TD, Kelley BP, Nicholls A, Warren SD: Essential considerations for using protein-ligand structures in drug discovery. Drug Discov Today. 2012, 17: 1270-1281. 10.1016\/j.drudis.2012.06.011.","journal-title":"Drug Discov Today"},{"key":"476_CR29","unstructured":"UniProtKB. http:\/\/www.uniprot.org\/help\/uniprotkb,"},{"key":"476_CR30","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1107\/S0907444910045749","volume":"67","author":"MD Winn","year":"2011","unstructured":"Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, Evans PR, Keegan RM, Krissinel EB, Leslie AGW, McCoy A, McNicholas SJ, Murshudov GN, Pannu NS, Potterton EA, Powell HR, Read RJ, Vagin A, Wilson KS: Overview of the CCP4 suite and current developments. Acta Crystallogr Sect D Biol Cryst. 2011, 67: 235-42. 10.1107\/S0907444910045749.","journal-title":"Acta Crystallogr Sect D Biol Cryst"},{"key":"476_CR31","volume-title":"The PyMOL Molecular Graphics System","author":"L Schr\u00f6dinger","year":"2010","unstructured":"Schr\u00f6dinger L: The PyMOL Molecular Graphics System. 2010"},{"key":"476_CR32","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1002\/prot.10104","volume":"47","author":"E Krieger","year":"2002","unstructured":"Krieger E, Koraimann G, Vriend G: Increasing the precision of comparative models with YASARA NOVA\u2013a self-parameterizing force field. Proteins. 2002, 47: 393-402. 10.1002\/prot.10104.","journal-title":"Proteins"},{"issue":"Suppl 9","key":"476_CR33","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1002\/prot.22570","volume":"77","author":"E Krieger","year":"2009","unstructured":"Krieger E, Joo K, Lee J, Lee J, Raman S, Thompson J, Tyka M, Baker D, Karplus K: Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: Four approaches that performed well in CASP8. Proteins. 2009, 77 (Suppl 9): 114-22.","journal-title":"Proteins"},{"key":"476_CR34","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1006\/jmbi.1998.2051","volume":"282","author":"S Vos","year":"1998","unstructured":"Vos S, Parry RJ, Burns MR, De Jersey J, Martin JL: Structures of free and complexed forms of Escherichia coli xanthine-guanine phosphoribosyltransferase. J Mole Biol. 1998, 282: 875-89. 10.1006\/jmbi.1998.2051.","journal-title":"J Mole Biol"},{"key":"476_CR35","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1021\/jm061277y","volume":"50","author":"MJ Hartshorn","year":"2007","unstructured":"Hartshorn MJ, Verdonk ML, Chessari G, Brewerton SC, Mooij WTM, Mortenson PN, Murray CW: Diverse, high-quality test set for the validation of protein-ligand docking performance. J Med Chem. 2007, 50: 726-41. 10.1021\/jm061277y.","journal-title":"J Med Chem"}],"container-title":["Journal of Cheminformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1758-2946-5-36.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1758-2946-5-36\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1758-2946-5-36.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:49:36Z","timestamp":1630543776000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcheminf.biomedcentral.com\/articles\/10.1186\/1758-2946-5-36"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,29]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["476"],"URL":"https:\/\/doi.org\/10.1186\/1758-2946-5-36","relation":{},"ISSN":["1758-2946"],"issn-type":[{"value":"1758-2946","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,29]]},"assertion":[{"value":"15 May 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"36"}}