title: Molecular dynamics simulations of the helical antimicrobial peptide ovispirin-1 in a zwitterionic dodecylphosphocholine micelle: insights into host-cell toxicity.
abstract: We have carried out a 40-ns all-atom molecular dynamics simulation of the helical antimicrobial peptide ovispirin-1 (OVIS) in a zwitterionic diphosphocholine (DPC) micelle. The DPC micelle serves as an economical and effective model for a cellular membrane owing to the presence of a choline headgroup, which resembles those of membrane phospholipids. OVIS, which was initially placed along a micelle diameter, diffuses out to the water-DPC interface, and the simulation stabilizes to an interface-bound steady state in 40 ns. The helical content of the peptide marginally increases in the process. The final conformation, orientation, and the structure of OVIS are in excellent agreement with the experimentally observed properties of the peptide in the presence of lipid bilayers composed of 75% zwitterionic lipids. The amphipathic peptide binds to the micelle with its hydrophobic face buried in the micellar core and the polar side chains protruding into the aqueous phase. There is overwhelming evidence that points to the significant and indispensable participation of hydrophobic residues in binding to the zwitterionic interface. The simulation starts with a conformation that is unbiased toward the final experimentally known binding state of the peptide. The ability of the model to reproduce experimental binding states despite this starting conformation is encouraging.
authors.affiliation: Department of Chemical Engineering and Materials Science and The Digital Technology Center, University of Minnesota, 421 Washington Avenue Southeast, Minneapolis, Minnesota 55455, USA.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Khandelia
authors.forename: Yiannis N
authors.initials: YN
authors.lastname: Kaznessis
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008823:Micelles; D008954:Models, Biological; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008081:Liposomes; D008823:Micelles; C440189:ovispirin; D010767:Phosphorylcholine; C028810:dodecylphosphocholine