Identifying of potential drugs for inhibition the M2 protein channel of influenza a by steered molecular dynamics

Abstract

Combining Lipinski’s rule and docking method were used as a virtual screening tool to find out top hits from the large data base CHEMSPIDER with more than 1.4 million compounds. The lowest binding energy ΔE_bind obtained in the best docking mode was chosen as a scoring function for selecting top ligands. Virtual screening has obtained top-leads compounds with binding energy less than -11.0 kcal.mol^-1 for inhibition the M2 protein channels of influenza A virus H5N1. Since the predictive power of the docking method is limited, top-leads were selected for further study by the more precise steered molecular dynamics method. The main idea of this method is that instead of the binding free energy, the rupture force needed to unbind a ligand from a receptor used as a measure of binding affinity. The higher is rupture force, and the stronger is binding.