Title: A computational approach to predict the possible binding site of HCV NS5A and the host cell chaperone, GRP78

Abstract

Aim: Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum located chaperone that plays a vital role during cellular stress. NS5A is one of the hepatitis C virus (HCV) non-structural proteins essential for replication. Materials & methods: Protein–protein docking was used to test the binding mode between GRP78 and HCV NS5A. Molecular dynamics simulations (MDSs) are performed on HCV NS5A, GRP78 and the HCV NS5A–GRP78 complex. Results: Docking and MDS reveal the ability of the GRP78 substrate-binding domain β to associate tightly with the HCV NS5A C142-C165 region. Conclusion: MDS reveals the potential of the C142-C165 region of the HCV NS5A to be used as a seed to develop a recognition inhibitor that counterparts the viral protein recognition by GRP78.