title: Membrane insertion of fusion peptides from Ebola and Marburg viruses studied by replica-exchange molecular dynamics simulations.
abstract: This work presents replica-exchange molecular dynamics simulations of inserting a 16-residue Ebola virus fusion peptide into a membrane bilayer. A computational approach is applied for modeling the peptide at the explicit all-atom level and the membrane-aqueous bilayer by a generalized Born continuum model with a smoothed switching function (GBSW). We provide an assessment of the model calculations in terms of three metrics: (1) the ability to reproduce the NMR structure of the peptide determined in the presence of SDS micelles and comparable structural data on other fusion peptides; (2) determination of the effects of the mutation Trp-8 to Ala and sequence discrimination of the homologous Marburg virus; and (3) calculation of potentials of mean force for estimating the partitioning free energy and their comparison to predictions from the Wimley-White interfacial hydrophobicity scale. We found the GBSW implicit membrane model to produce results of limited accuracy in conformational properties of the peptide when compared to the NMR structure, yet the model resolution is sufficient to determine the effect of sequence differentiation on peptide-membrane integration. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Cell Biology and Biochemistry, Molecular and Translational Sciences, USAMRIID, Fredrick, Maryland.
authors.forename: Mark A
authors.identifier: 0000-0002-5259-0343
authors.initials: MA
authors.lastname: Olson
authors.affiliation: Computational Sciences Division, U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Defense Biotechnology High Performance Computing Software Applications Institute, U.S. Army Medical Research and Materiel Command, Fredrick, Maryland.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Yeh
mesh_terms: D000595:Amino Acid Sequence; D029043:Ebolavirus / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D029024:Marburgvirus / Q000737:chemistry*; D050576:Membrane Fusion Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics; D014760:Viral Fusion Proteins / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D050576:Membrane Fusion Proteins; D010455:Peptides; D014760:Viral Fusion Proteins; D014867:Water
keywords: free-energy landscape; molecular dynamics; peptide-membrane dynamics; replica exchange