Ensemble-based virtual screening of human PI4KIIIα inhibitors toward the Hepatitis C virus

Abstract

The consideration of flexibility of protein structures in virtual screening still remains a challenge. In this work, an ensemble-based virtual screening method considering the dynamics and flexibility of the receptor protein is proposed. Representative structures of receptor protein are extracted from molecular dynamics simulations adopted to sample the protein’s conformational space, and used for the virtual screening in addition to the crystal structure. Ten potential inhibitors for PI4KIIIα were identified and MM/GBSA method was used to calculate the binding free energies and indentify the selective mechanisms. The method is expected to provide useful insights into the drug design.