Publication
Selective flexibility of side-chain residues improves VEGFR-2 docking score using AutoDock Vina
| dc.contributor.author | Abreu, Rui M.V. | |
| dc.contributor.author | Froufe, Hugo J.C. | |
| dc.contributor.author | Queiroz, Maria João R.P. | |
| dc.contributor.author | Ferreira, Isabel C.F.R. | |
| dc.date.accessioned | 2012-08-21T14:53:31Z | |
| dc.date.available | 2012-08-21T14:53:31Z | |
| dc.date.issued | 2012 | |
| dc.description.abstract | Selective side-chain residue flexibility is an option available on AutoDock Vina docking software. This approach is promising as it attempts to provide a more realistic ligand-protein interaction environment, without an unmanageable increase in computer processing time. However, studies validating this approach are still scarce. VEGFR-2 (vascular endothelial growth factor receptor 2), a known protein target for antiangiogenic agents, was used in this study. Four residues present in the VEGFR-2 kinase site were selected and made flexible: Lys866, Glu885, Cys917 and Asp1044. The docking scores for all possible combinations of flexible residues were compared to the docking scores using a rigid conformation. The best overall docking scores were obtained using the Glu883 flexible conformation, with pearson and spearman rank correlation values of 0.568 and 0.543, respectively, and a 51% increase in computer processing time. Using different VEGFR-2 X-ray structures a similar trend was observed with Glu885 flexible conformation presenting the best scores. This study demonstrates that careful use of selective side-chain residue flexibility can improve AutoDock Vina docking score accuracy, without a significant increase in computer processing time. This methodology proved to be a valuable tool in drug design when using VEGFR-2 but will also probably be useful if applied to other protein targets. | por |
| dc.identifier.citation | Abreu, Rui M.V.; Froufe, Hugo J.C.; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R. (2012). Selective flexibility of side-chain residues improves VEGFR-2 docking score using AutoDock Vina. Chemical Biology & Drug Design. ISSN 1747-0277. 79:4, p. 530-534 | por |
| dc.identifier.doi | 10.1111/j.1747-0285.2011.01313.x | |
| dc.identifier.issn | 1747-0277 | |
| dc.identifier.uri | http://hdl.handle.net/10198/7377 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Wiley | por |
| dc.relation | SFRH/PROTEC/49450/2009 | |
| dc.subject | aa residue flexibility | por |
| dc.subject | Docking | por |
| dc.subject | Drug design | por |
| dc.subject | VEGFR-2 | por |
| dc.subject | Virtual screening | por |
| dc.title | Selective flexibility of side-chain residues improves VEGFR-2 docking score using AutoDock Vina | por |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FQUI-QUI%2F111060%2F2009/PT | |
| oaire.citation.endPage | 539 | por |
| oaire.citation.startPage | 530 | por |
| oaire.citation.title | Chemical Biology & Drug Design | por |
| oaire.citation.volume | 79 | por |
| oaire.fundingStream | 5876-PPCDTI | |
| person.familyName | Abreu | |
| person.familyName | Ferreira | |
| person.givenName | Rui M.V. | |
| person.givenName | Isabel C.F.R. | |
| person.identifier | 144781 | |
| person.identifier.ciencia-id | 0F19-0DE2-12A2 | |
| person.identifier.ciencia-id | 9418-CF95-9919 | |
| person.identifier.orcid | 0000-0002-7745-8015 | |
| person.identifier.orcid | 0000-0003-4910-4882 | |
| person.identifier.rid | E-8500-2013 | |
| person.identifier.scopus-author-id | 7003290613 | |
| person.identifier.scopus-author-id | 36868826600 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | openAccess | por |
| rcaap.type | article | por |
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