Exponential repulsion improves structural predictability of molecular docking.
Molecular docking is a powerful tool for theoretical prediction of the preferred conformation and orientation of small molecules within protein active sites. The obtained poses can be used for estimation of binding energies, which indicate the inhibition effect of designed inhibitors, and therefore might be used for in silico drug design. However, the evaluation of ligand binding affinity critically depends on successful prediction of the native binding mode. Contemporary docking methods are often based on scoring functions derived from molecular mechanical potentials. In such potentials, nonbonded interactions are typically represented by electrostatic interactions between atom-centered partial charges and standard 6-12 Lennard-Jones potential. Here, we present implementation and testing of a scoring function based on more physically justified exponential repulsion instead of the standard Lennard-Jones potential. We found that this scoring function significantly improved prediction of the native binding modes in proteins bearing narrow active sites such as serine proteases and kinases. © 2016 Wiley Periodicals, Inc.
Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR & Palacky University, Šlechtitelů 11, Olomouc, 783 71, Czech Republic.|Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, Olomouc, 77146, Czech Republic.
Václav
V
Bazgier
Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, Olomouc, 77146, Czech Republic.
Karel
K
Berka
Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, Olomouc, 77146, Czech Republic.
Michal
M
Otyepka
Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University Olomouc, 17. listopadu 12, Olomouc, 77146, Czech Republic. pavel.banas@upol.cz.
Pavel
P
Banáš
DOCK 6.6; cyclin-dependent kinase 2; directory of decoys; drug design; molecular docking