Dynamics and binding interactions of peptide inhibitors of dengue virus entry

Mohd Isa, Diyana and Chin, Sek Peng and Chong, Wei Lim and Zain, Sharifuddin Md and Abd Rahman, Noorsaadah and Lee, Vannajan Sanghiran (2019) Dynamics and binding interactions of peptide inhibitors of dengue virus entry. Journal of Biological Physics, 45 (1). pp. 63-76. ISSN 0092-0606, DOI https://doi.org/10.1007/s10867-018-9515-6.

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Official URL: https://doi.org/10.1007/s10867-018-9515-6


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. © 2019, Springer Nature B.V.

Item Type: Article
Funders: Faculty Research Grant, University Malaya (GPF062B-2018)
Uncontrolled Keywords: Antiviral peptides; DENV2; Molecular docking; Molecular dynamics simulations
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 23 Mar 2020 04:16
Last Modified: 04 Aug 2020 02:13
URI: http://eprints.um.edu.my/id/eprint/24097

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