Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry


Molecular docking study on Hemagglutinin protein of H1N1 virus with recommended antiviral drugs

Author(s): Vijay Tripathi, Richa Sinha, Dwijendra Kumar Gupta

Molecular docking is routinely used for understanding drug–receptor interaction in modern drug design. The goal of protein docking is to obtain a model for the bound complex from the coordinates of the unbound component molecules. Current docking methods evaluate a vast number of docked conformations by simple functions that measure surface complementarily. Many proteins undergo small side chain or even backbone movements on binding of different ligands into the same protein structure. This is known as induced fit and is potentially problematic for virtual screening of databases against protein targets. In this report we investigate the limits of the flexible protein approximation used by the docking program, AutoDock, through cross-docking using protein structures of influenza hemagglutinin. Here, we describe the suitability of antiviral drugs recommended against influenza for the docking and 3D structure prediction of hemagglutinin protein of the novel influenza A virus H1N1. The 3D structure of the macromolecular complex resulting from the protein-ligand association is a very useful basis to understand its specific functions. Homology model of hemagglutinin protein was constructed using MODELLER 9v6 and the model was energy minimized and validated using Gromacs to obtain a stable structure, which was further used for 3D structure prediction and docking through molecular docking studies using Autodock. The active sites were analyzed by the program Surface Racer.