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Molecular Docking and Molecular Dynamics Simulation Studies to Predict Flavonoid Binding on the Surface of DENV2 E Protein

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Abstract

Dengue infections are currently estimated to be 390 million cases annually. Yet, there is no vaccine or specific therapy available. Envelope glycoprotein E (E protein) of DENV mediates viral attachment and entry into the host cells. Several flavonoids have been shown to inhibit HIV-1 and hepatitis C virus entry during the virus–host membrane fusion. In this work, molecular docking method was employed to predict the binding of nine flavonoids (baicalin, baicalein, EGCG, fisetin, glabranine, hyperoside, ladanein, quercetin and flavone) to the soluble ectodomain of DENV type 2 (DENV2) E protein. Interestingly, eight flavonoids were found to dock into the same binding pocket located between the domain I and domain II of different subunits of E protein. Consistent docking results were observed not only for the E protein structures of the DENV2-Thai and DENV2-Malaysia (a homology model) but also for the E protein structures of tick-borne encephalitis virus and Japanese encephalitis virus. In addition, molecular dynamics simulations were performed to further evaluate the interaction profile of the docked E protein–flavonoid complexes. Ile4, Gly5, Asp98, Gly100 and Val151 residues of the DENV2-My E protein that aligned to the same residues in the DENV2-Thai E protein form consistent hydrogen bond interactions with baicalein, quercetin and EGCG during the simulations. This study demonstrates flavonoids potentially form interactions with the E protein of DENV2.

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Acknowledgments

The authors thank Dr. Ozlem Demir for the helpful discussion and careful reading of the manuscript. This research was supported by the Universiti Teknologi MARA (UiTM) Dana Cluster 600-RMI/DANA 5/3/CG (2/2012). NAI was funded by the scholarship from the Ministry of Higher Education (Malaysia) through the MyBrain15 program. We thank Faculty of Pharmacy, UiTM Puncak Alam Campus for providing the computing facilities in the Bioinformatics Lab, as well as Research Management Institute (RMI), UiTM and Ministry of Science and Technology Malaysia (MOSTI) for the financial and administrative support.

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  1. Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300, Bandar Puncak Alam, Malaysia

    Nurul Azira Ismail & Siti Azma Jusoh

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  1. Nurul Azira Ismail
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Correspondence to Siti Azma Jusoh.

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Ismail, N.A., Jusoh, S.A. Molecular Docking and Molecular Dynamics Simulation Studies to Predict Flavonoid Binding on the Surface of DENV2 E Protein. Interdiscip Sci Comput Life Sci 9, 499–511 (2017). https://doi.org/10.1007/s12539-016-0157-8

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