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

Authors

  • Yeng-Tseng Wang,

    Corresponding author
    1. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, R.O.C
    • Department of Biochemistry, College of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, R.O.C

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  • Yu-Ching Chen

    1. Department of Biomedical Informatics of Asia University, No. 500, Lioufeng Road, Wufeng, Taichung 41354, Taiwan R.O.C
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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.

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