Affiliations 

  • 1 Drug Design & Development Research Group, University of Malaya, 50603 Kuala Lumpur, Malaysia; Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 2 Drug Design & Development Research Group, University of Malaya, 50603 Kuala Lumpur, Malaysia; Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 3 Drug Design & Development Research Group, University of Malaya, 50603 Kuala Lumpur, Malaysia; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 4 School of Chemistry and Chemical Engineering, Queen's University Belfast, Northern Ireland, United Kingdom; School of Biomedical Engineering, Xinxiang Medical University, Xinxiang, Henan 453003, China
  • 5 School of Chemistry and Chemical Engineering, Queen's University Belfast, Northern Ireland, United Kingdom
  • 6 Drug Design & Development Research Group, University of Malaya, 50603 Kuala Lumpur, Malaysia; Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre for Natural Product Research and Drug Discovery, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: rozanaothman@um.edu.my
J Mol Graph Model, 2017 06;74:273-287.
PMID: 28458006 DOI: 10.1016/j.jmgm.2017.03.010

Abstract

Effective novel peptide inhibitors which targeted the domain III of the dengue envelope (E) protein by blocking dengue virus (DENV) entry into target cells, were identified. The binding affinities of these peptides towards E-protein were evaluated by using a combination of docking and explicit solvent molecular dynamics (MD) simulation methods. The interactions of these complexes were further investigated by using the Molecular Mechanics-Poisson Boltzmann Surface Area (MMPBSA) and Molecular Mechanics Generalized Born Surface Area (MMGBSA) methods. Free energy calculations of the peptides interacting with the E-protein demonstrated that van der Waals (vdW) and electrostatic interactions were the main driving forces stabilizing the complexes. Interestingly, calculated binding free energies showed good agreement with the experimental dissociation constant (Kd) values. Our results also demonstrated that specific residues might play a crucial role in the effective binding interactions. Thus, this study has demonstrated that a combination of docking and molecular dynamics simulations can accelerate the identification process of peptides as potential inhibitors of dengue virus entry into host cells.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.