Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/22008
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Campo DC | Valor | Idioma |
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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 | 2012-12-21T16:12:29Z | - |
dc.date.available | 2012-12-21T16:12:29Z | - |
dc.date.issued | 2012 | - |
dc.date.submitted | 2011-04-22 | - |
dc.identifier.issn | 1747-0277 | por |
dc.identifier.uri | https://hdl.handle.net/1822/22008 | - |
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 anti-angiogenic 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.description.sponsorship | The authors are grateful to Foundation for Science and Technology (Portugal) and COMPETE/QREN/EU for financial support through research project PTDC/QUI-QUI/111060/2009 and Rui M.V. Abreu thanks to SFRH/PROTEC/49450/2009 grant. | por |
dc.language.iso | eng | por |
dc.publisher | John Wiley and Sons | por |
dc.rights | openAccess | por |
dc.subject | Drug design | por |
dc.subject | Virtual screening | por |
dc.subject | Aa residues flexibility | por |
dc.subject | VEGFR-2 | por |
dc.subject | aa residue flexibility | por |
dc.subject | docking | por |
dc.title | Selective flexibility of side-chain residues improves VEGFR-2 docking score using autodock vina | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | www.wiley.com | por |
sdum.publicationstatus | published | por |
oaire.citationStartPage | 530 | por |
oaire.citationEndPage | 534 | por |
oaire.citationIssue | 4 | por |
oaire.citationTitle | Chemical Biology & Drug Design | por |
oaire.citationVolume | 79 | por |
dc.identifier.doi | 10.1111/j.1747-0285.2011.01313.x | por |
dc.identifier.pmid | 22188672 | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Chemical Biology & Drug Design | por |
Aparece nas coleções: | CDQuim - Artigos (Papers) |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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CBDD-revised2012.pdf | Documento principal aceite e revisto para publicação | 289,18 kB | Adobe PDF | Ver/Abrir |