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TitleSelective flexibility of side-chain residues improves VEGFR-2 docking score using autodock vina
Author(s)Abreu, Rui M. V.
Froufe, Hugo J. C.
Queiroz, Maria João R. P.
Ferreira, Isabel C. F. R.
KeywordsDrug design
Virtual screening
Aa residues flexibility
aa residue flexibility
Issue date2012
PublisherJohn Wiley and Sons
JournalChemical Biology & Drug Design
Abstract(s)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.
AccessOpen access
Appears in Collections:CDQuim - Artigos (Papers)

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