Interdisciplinary Sciences: Computational Life Sciences

pp 1–13

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

Original Research Article

DOI: 10.1007/s12539-016-0157-8

Cite this article as:
Ismail, N.A. & Jusoh, S.A. Interdiscip Sci Comput Life Sci (2016). doi:10.1007/s12539-016-0157-8

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.

Keywords

Dengue virus MalaysiaDENV2FlavonoidsBaicalinBaicaleinEGCGFisetinGlabranineHyperosideLadaneinQuercetinDockingMolecular dynamics simulationsEnvelope glycoprotein E

Supplementary material

12539_2016_157_MOESM1_ESM.pdf (1.3 mb)
Supplementary material 1 (PDF 1303 kb)

Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Pharmaceutical Life Sciences, Faculty of PharmacyUniversiti Teknologi MARABandar Puncak AlamMalaysia