N1 neuraminidase of H5N1 avian influenza A virus complexed with sialic acid and zanamivir – A study by molecular docking and molecular dynamics simulation

Abstract

Development of antiviral drugs is an urgent need to control and prevent the presently circulating H5N1 avian influenza virus which is affects the human respiratory tract. The complex crystal structure of N1–N–acetylneuranamic acid (sialic acid, SIA) is not available as complex and hence SIA and zanamivir (ZMR) are docked into the binding site of N1 neuraminidase. Based on the analysis, the initial complex structures have been simulated for 120 ns to get insight into the binding modes and interaction between protein–ligand complex systems. NAMD pair interaction energy and MM–PBSA binding free energy are calculated and show that there are two possible binding modes (BM1 and BM2) for N1–SIA and a single binding mode (BM1) for and N1–ZMR complex structures respectively. BM1 of N1–SIA is the most preferred binding mode. On contrary to the currently available drugs in which the chair conformation is distorted, in both the binding modes of N1–SIA, the binding pocket of N1 neuraminidase is able to accommodate SIA in 2C5 chair conformation which is the preferred conformation of SIA in solution state. In N1–ZMR complex, ZMR is bind in a distorted chair conformation. The neuraminidase binding pocket is also able to accommodate galactose of SIAα(2→3)GAL and SIAα(2→6)GAL. RMSD, RMSF and hydrogen bonding analyses have been carried out to identify the conformational flexibility and structural stability of each complex system. All the analyses show that SIA can be used as an inhibitor for N1 neuraminidase of H5N1 influenza viral infection. Communicated by Ramaswamy H. Sarma