A simulation investigation on interaction mechanism between Ebola nucleoprotein and VP35 peptide

Ebola viruses (EBOV) will induce acute hemorrhagic fever, which is fatal to humans and nonhuman primates. The combination of EBOV VP35 peptide with nucleoprotein N-terminal (NPNTD) is proposed based on static crystal structures in recent studies, but VP35 binding mechanism and conformational dynamic...

Full description

Saved in:
Bibliographic Details
Published in:Journal of biomolecular structure & dynamics 2018-03, Vol.36 (4), p.1009-1028
Main Authors: Ding, Jing-Na, Zhang, Yan-Jun, Zhong, Hui, Ao, Cheng-Cheng, Han, Ju-Guang
Format: Article
Language:English
Subjects:
binding mechanisms
Binding Sites
Crystallography, X-Ray
Ebolavirus - chemistry
Ebolavirus - genetics
EBOV nucleoprotein
Hemorrhagic Fever, Ebola - genetics
Hemorrhagic Fever, Ebola - virology
Humans
MD simulation
Molecular Dynamics Simulation
mutations
Nucleoproteins - chemistry
Nucleoproteins - genetics
Peptides - chemistry
Protein Binding
Protein Conformation
Viral Core Proteins - chemistry
Viral Core Proteins - genetics
VP35 peptide
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ebola viruses (EBOV) will induce acute hemorrhagic fever, which is fatal to humans and nonhuman primates. The combination of EBOV VP35 peptide with nucleoprotein N-terminal (NPNTD) is proposed based on static crystal structures in recent studies, but VP35 binding mechanism and conformational dynamics are still unclear. This investigation, using Molecular Dynamic (MD) simulation and Molecular Mechanics Generalized Born Surface Area (MM-GB/SA) energy calculation, more convincingly proves the greater roles of the protein binding mechanisms than do hints from the static crystal structure observations. Conformational analysis of the systems demonstrate that combination with VP35 may lead to the conformational transition of NPNTD from "open" to "closed" state. According to the analyses of binding free energies and their decomposition, VP35 residue R37 plays a crucial role in wild type as well as mutant systems. Mutations of I29 and L33 to aspartate as well as M34 to proline affect binding affinity mainly through influencing electrostatic interaction, which is closely related to H-bonds formation. In addition, mutations mainly affect β-hairpin and loop regions, among which, M34P may have the greatest influence to the binding. This study may provide specific binding mechanisms between VP35 peptide and NPNTD, especially some important residues concerning binding.
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2017.1307143