Insights from QM/MM Modeling the 3D Structure of the 2009 H1N1 Influenza A Virus Neuraminidase and Its Binding Interactions with Antiviral Drugs

Yeng-Tseng Wang; Yu-Ching Chen

doi:10.1002/minf.201300117

Insights from QM/MM Modeling the 3D Structure of the 2009 H1N1 Influenza A Virus Neuraminidase and Its Binding Interactions with Antiviral Drugs

Mol Inform. 2014 Mar;33(3):240-9. doi: 10.1002/minf.201300117. Epub 2014 Mar 11.

Authors

Yeng-Tseng Wang¹, Yu-Ching Chen²

Affiliations

¹ Department of Biochemistry, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, R.O.C. c00jsw00@gmail.com.
² Department of Biomedical Informatics of Asia University, No. 500, Lioufeng Road, Wufeng, Taichung 41354, Taiwan R.O.C.

PMID: 27485692
DOI: 10.1002/minf.201300117

Abstract

Control of drug release through the inhibition of neuraminidase-1 has been identified as a potential target for the treatment of H1N1 influenza; however, the drug binding mode of neuraminidase is not yet completely understood. In this work, we propose a model for a neuraminidase-1 complex based on four known X-ray structures of drug/neuraminidase-1 complexes. Specifically, H1N1 neuraminidase-1 complexed with 4 drugs (zanamivir, laninamivir, laninamivir octanoate and oseltamivir) was first investigated using a combined quantum mechanical and molecular mechanical (QM/MM) approach. Based on these structures, a model for the H1N1 neuraminidase-1 complex was proposed and simulated using the same computational protocol. Implications to drug/H1N1 neuraminidase-1 binding modes are discussed. From our simulations, the predicted binding free energies of the four drugs are in good agreement with the experimental results, with the correlation coefficient being 0.84.

Keywords: H1N1; MMPBSA; Molecular dynamics; Neuramindase; QMMM.