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|Title:||Selective 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.
Aa residues flexibility
aa residue flexibility
|Publisher:||John Wiley and Sons|
|Journal:||Chemical 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.|
|Appears in Collections:||CDQuim - Artigos (Papers)|
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