title: A simulation investigation on interaction mechanism between Ebola nucleoprotein and VP35 peptide.
abstract: 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.
authors.affiliation: a National Synchrotron Radiation Laboratory , University of Science and Technology of China , Hefei 230029 , People's Republic of China.|b Department of Clinical Medicine , Anqing Medical College , Anqing 246052 , People's Republic of China.
authors.forename: Jing-Na
authors.initials: JN
authors.lastname: Ding
authors.affiliation: a National Synchrotron Radiation Laboratory , University of Science and Technology of China , Hefei 230029 , People's Republic of China.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: a National Synchrotron Radiation Laboratory , University of Science and Technology of China , Hefei 230029 , People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.affiliation: a National Synchrotron Radiation Laboratory , University of Science and Technology of China , Hefei 230029 , People's Republic of China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Ao
authors.affiliation: a National Synchrotron Radiation Laboratory , University of Science and Technology of China , Hefei 230029 , People's Republic of China.
authors.forename: Ju-Guang
authors.initials: JG
authors.lastname: Han
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D029043:Ebolavirus / Q000737:chemistry* / Q000235:genetics; D019142:Hemorrhagic Fever, Ebola / Q000235:genetics / Q000821:virology*; D006801:Humans; D056004:Molecular Dynamics Simulation; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry* / Q000235:genetics; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D014758:Viral Core Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D014758:Viral Core Proteins; C084818:nucleoprotein VP35, Ebola virus
keywords: EBOV nucleoprotein; MD simulation; VP35 peptide; binding mechanisms; mutations