Structure Prediction and Active Site Analysis of New H1N1 Neuraminidase:Target for Antiviral Drug Design

Abstract

The H1N1 viral envelope protein neuraminidase encoded by NA gene plays a key role in the pathogenesis of swine flu. The active site of the neuraminidase protein is targeted by presently available antiviral drugs. The influenza virus often proves to be resistant to currently available drugs, due single amino acid substitutions conferred by the mutations in the gene coding for neuraminidase protein. The latest Influenza A virus A/Perth/262/2009(H1N1) sequence with accession number ADJ67981 was selected from NCBI. The BLAST program was used to identify the best template structure, which was found to be 3NSS_A. Sequence alignment was carried out with the template and query sequence, the identity and similarity was found to be 81.9% and 82.6% respectively. Homology modeling was performed using Accelrys Discovery Studio 3.5 software, the model with the lowest energy was then assessed for stereochemical quality and side-chain environment. The PDF energy and DOPE score of the best modeled structure was 2090.1682 and -43752.3632 respectively. Further active site optimization of the modeled protein was performed by molecular dynamics. The key active site residues which are crucial for further docking studies were ascertained.