Dynamics and binding interactions of peptide inhibitors of dengue virus entry

  • Diyana Mohd Isa
  • Sek Peng Chin
  • Wei Lim Chong
  • Sharifuddin M. Zain
  • Noorsaadah Abd Rahman
  • Vannajan Sanghiran LeeEmail author
Original Paper


In this study, we investigate the binding interactions of two synthetic antiviral peptides (DET2 and DET4) on type II dengue virus (DENV2) envelope protein domain III. These two antiviral peptides are designed based on the domain III of the DENV2 envelope protein, which has shown significant inhibition activity in previous studies and can be potentially modified further to be active against all dengue strains. Molecular docking was performed using AutoDock Vina and the best-ranked peptide-domain III complex was further explored using molecular dynamics simulations. Molecular mechanics-Poisson–Boltzmann surface area (MM-PBSA) was used to calculate the relative binding free energies and to locate the key residues of peptide–protein interactions. The predicted binding affinity correlated well with the previous experimental studies. DET4 outperformed DET2 and is oriented within the binding site through favorable vdW and electrostatic interactions. Pairwise residue decomposition analysis has revealed several key residues that contribute to the binding of these peptides. Residues in DET2 interact relatively lesser with the domain III compared to DET4. Dynamic cross-correlation analysis showed that both the DET2 and DET4 trigger different dynamic patterns on the domain III. Correlated motions were seen between the residue pairs of DET4 and the binding site while binding of DET2 results in anti-correlated motion on the binding site. This work showcases the use of computational study in elucidating and explaining the experiment observation on an atomic level.


DENV2 Antiviral peptides Molecular dynamics simulations Molecular docking 



The authors thank Hadieh Monajemi for her diligent proofreading of this paper. This research supported financially by Faculty Research Grant, University Malaya (GPF062B-2018).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

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ESM 1 (MPG 4165 kb)
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ESM 2 (MPG 3655 kb)


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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia

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