Original Research Article

Interdisciplinary Sciences: Computational Life Sciences

pp 1-13

First online:

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

  • Nurul Azira IsmailAffiliated withDepartment of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA
  • , Siti Azma JusohAffiliated withDepartment of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA Email author 

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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.

Keywords

Dengue virus Malaysia DENV2 Flavonoids Baicalin Baicalein EGCG Fisetin Glabranine Hyperoside Ladanein Quercetin Docking Molecular dynamics simulations Envelope glycoprotein E