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.
