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Dynamics and binding interactions of peptide inhibitors of dengue virus entry

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 inhibit...

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Main Authors: Mohd Isa, Diyana, Chin, Sek Peng, Chong, Wei Lim, Zain, Sharifuddin Md, Abd Rahman, Noorsaadah, Lee, Vannajan Sanghiran
Format: Article
Published: Springer 2019
Subjects:
Q Science (General)
QD Chemistry
Online Access:http://eprints.um.edu.my/24097/
https://doi.org/10.1007/s10867-018-9515-6
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spelling my.um.eprints.240972020-08-04T02:13:49Z http://eprints.um.edu.my/24097/ Dynamics and binding interactions of peptide inhibitors of dengue virus entry Mohd Isa, Diyana Chin, Sek Peng Chong, Wei Lim Zain, Sharifuddin Md Abd Rahman, Noorsaadah Lee, Vannajan Sanghiran Q Science (General) QD Chemistry 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. Springer 2019 Article PeerReviewed 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 https://doi.org/10.1007/s10867-018-9515-6 doi:10.1007/s10867-018-9515-6
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic Q Science (General)
QD Chemistry
spellingShingle Q Science (General)
QD Chemistry
Mohd Isa, Diyana
Chin, Sek Peng
Chong, Wei Lim
Zain, Sharifuddin Md
Abd Rahman, Noorsaadah
Lee, Vannajan Sanghiran
Dynamics and binding interactions of peptide inhibitors of dengue virus entry
description 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.
format Article
author Mohd Isa, Diyana
Chin, Sek Peng
Chong, Wei Lim
Zain, Sharifuddin Md
Abd Rahman, Noorsaadah
Lee, Vannajan Sanghiran
author_facet Mohd Isa, Diyana
Chin, Sek Peng
Chong, Wei Lim
Zain, Sharifuddin Md
Abd Rahman, Noorsaadah
Lee, Vannajan Sanghiran
author_sort Mohd Isa, Diyana
title Dynamics and binding interactions of peptide inhibitors of dengue virus entry
title_short Dynamics and binding interactions of peptide inhibitors of dengue virus entry
title_full Dynamics and binding interactions of peptide inhibitors of dengue virus entry
title_fullStr Dynamics and binding interactions of peptide inhibitors of dengue virus entry
title_full_unstemmed Dynamics and binding interactions of peptide inhibitors of dengue virus entry
title_sort dynamics and binding interactions of peptide inhibitors of dengue virus entry
publisher Springer
publishDate 2019
url http://eprints.um.edu.my/24097/
https://doi.org/10.1007/s10867-018-9515-6
_version_ 1674066715186561024
score 13.211869

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