title: Conformational sampling of influenza fusion peptide in membrane bilayers as a function of termini and protonation states.
abstract: Influenza fusion peptide is critical for mediating the fusion of viral and host cell membranes during viral entry. The interaction of monomeric influenza fusion peptide with membranes is studied with replica exchange molecular dynamics simulations using a new implicit membrane model to effectively reach microsecond to millisecond time scales. The conformational sampling of the fusion peptide was studied as a function of different N- and C-termini, including an experimental construct with an additional C-terminal tag, as well as a function of protonation of acidic residues. It is found that the influenza fusion peptide mostly adopts helical structures with a pronounced kink at residues 11-13 with both N-terminal and C-terminal helices oriented mostly parallel to the membrane surface. A charged C-terminus and the presence of a charge C-terminal tag significantly alters the conformational sampling of the fusion peptide and results in more diverse conformational ensembles that include obliquely inserted N-terminal peptide structures. Protonation of acidic residues also affects the conformational sampling, however, based on pK(a) shift estimates the overall effect of pH = 5 on the conformational sampling of the influenza fusion peptide appears to be only minor.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Afra
authors.initials: A
authors.lastname: Panahi
authors.forename: Michael
authors.initials: M
authors.lastname: Feig
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae; D010446:Peptide Fragments / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D011487:Protein Conformation; D011522:Protons; D013997:Time Factors; D014760:Viral Fusion Proteins / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; D011522:Protons; D014760:Viral Fusion Proteins