Molecular Dynamics Study On New Inhibitors Of Neuraminidase

Influenza is an infectious disease caused by influenza virus, which has a serious impact on human life and health. In recent years, H5N1 highly pathogenic avian influenza showing a spread trend, causing widespread concern in the world. Neuraminidase(NA) is a glycoprotein that on the surface of the influenza virus, it plays an important role in the replication of the influenza virus.It is an important target for the design of anti-influenza virus drugs. At present,the commonly used anti-influenza virus drugs have M2 ion channel inhibitors and NA inhibitors. The disadvantage of the former is that there is a rapid emergence of drug resistance and it only effective against influenza A virus.Oseltamivir, which is one of the NA inhibitors, plays a decisive role in preventing influenza virus. But with the emergence of drug resistance, the study of novel NA inhibitors is imminent.In this thesis, the interaction between oseltamivir and its derivatives with neuraminidase was studied using molecular docking and molecular dynamics simulation. The feasibility of molecular docking method was verified and the result shows that the docking software chosen and the docking parameters are suitable for the selected system. The docking results of oseltamivir and its derivatives with neuraminidase show that ligand and receptor formed stable complexes. During 50 ns simulation, the root mean square derivares(RMSD)trajectories of three complex systems could reach equilibrium states. All of these three ligands form stable hydrogen bonds with some important residues in the active site of neuraminidase. Moreover, the docking energies and binding free energies between these compounds and neuraminidase are in consistent with IC50 value of experiment assays. The amino acid residues near the neuraminidase active site such as ARG152, ARG292, ARG371 and TYR347 play an important role in the binding of inhibitors and neuraminidase. This article can providetheoretical reference to the design of new neuraminidase inhibitors, and may facilitate the development of influenza virus drug.