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Title: Selective flexibility of side-chain residues improves VEGFR-2 docking score using AutoDock Vina.
Authors: Abreu, Rui M.V.
Froufe, Hugo J.C.
Queiroz, Maria João R.P.
Ferreira, Isabel C.F.R.
Keywords: aa residue flexibility
Drug design
Virtual screening
Issue Date: 2012
Publisher: Wiley
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
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.
Peer review: yes
ISSN: 1747-0277
Appears in Collections:BB - Artigos em Revistas Indexados ao ISI/Scopus

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