title: Transmembrane domains of viral ion channel proteins: a molecular dynamics simulation study.
abstract: Nanosecond molecular dynamics simulations in a fully solvated phospholipid bilayer have been performed on single transmembrane alpha-helices from three putative ion channel proteins encoded by viruses: NB (from influenza B), CM2 (from influenza C), and Vpu (from HIV-1). alpha-Helix stability is maintained within a core region of ca. 28 residues for each protein. Helix perturbations are due either to unfavorable interactions of hydrophobic residues with the lipid headgroups or to the need of the termini of short helices to extend into the surrounding interfacial environment in order to form H-bonds. The requirement of both ends of a helix to form favorable interactions with lipid headgroups and/or water may also lead to tilting and/or kinking of a transmembrane alpha-helix. Residues that are generally viewed as poor helix formers in aqueous solution (e.g., Gly, Ile, Val) do not destabilize helices, if located within a helix that spans a lipid bilayer. However, helix/bilayer mismatch such that a helix ends abruptly within the bilayer core destabilizes the end of the helix, especially in the presence of Gly and Ala residues. Hydrogen bonding of polar side-chains with the peptide backbone and with one another occurs when such residues are present within the bilayer core, thus minimizing the energetic cost of burying such side-chains.
authors.affiliation: Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Rex Richards Building, South Parks Road, Oxford, OX1 3QU, UK. wolfgang@bioch.ox.ac.uk
authors.forename: W B
authors.initials: WB
authors.lastname: Fischer
authors.forename: L R
authors.initials: LR
authors.lastname: Forrest
authors.forename: G R
authors.initials: GR
authors.lastname: Smith
authors.forename: M S
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D006023:Glycoproteins / Q000737:chemistry; D015497:HIV-1; D054298:Human Immunodeficiency Virus Proteins; D006860:Hydrogen Bonding; D007091:Image Processing, Computer-Assisted; D009981:Influenza B virus; D009982:Gammainfluenzavirus; D007473:Ion Channels; D008051:Lipid Bilayers; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D014763:Viral Matrix Proteins / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry*; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D006023:Glycoproteins; D054298:Human Immunodeficiency Virus Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C090877:CM2 protein, Influenza C virus; C051094:NB glycoprotein, Influenza B virus; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins