In silico binding free energy predictability with pi-pi interaction energy-augmented scoring function: Benzimidazole Raf inhibitors as a case study

Abstract

The ability to estimate binding affinities of ligands precisely is of paramount importance in designing drugs. Docking programs are used primarily to predict the binding mode of ligands to receptors. However, current scoring functions as used in docking programs are not reliable enough to predict binding affinities of ligands without any further calculations. In the present study, we investigate the usefulness of adding pi-pi interaction energies between ring groups of residues and ligands to the scoring function for docking. It is found that such addition helps ranking ligand activities more correctly. LMP2 calculation is used to measure pi-pi interaction energies between ring groups. The result of this simple addition shows possibility of pi-pi interaction generalization in scoring functions. (C) 2012 Elsevier Ltd. All rights reserved.