title: Pores formed by the nicotinic receptor m2delta Peptide: a molecular dynamics simulation study.
abstract: The M2delta peptide self-assembles to form a pentameric bundle of transmembrane alpha-helices that is a model of the pore-lining region of the nicotinic acetylcholine receptor. Long (>15 ns) molecular dynamics simulations of a model of the M2delta(5) bundle in a POPC bilayer have been used to explore the conformational dynamics of the channel assembly. On the timescale of the simulation, the bundle remains relatively stable, with the polar pore-lining side chains remaining exposed to the lumen of the channel. Fluctuations at the helix termini, and in the helix curvature, result in closing/opening transitions at both mouths of the channel, on a timescale of approximately 10 ns. On average, water within the pore lumen diffuses approximately 4x more slowly than water outside the channel. Examination of pore water trajectories reveals both single-file and path-crossing regimes to occur at different times within the simulation.
authors.affiliation: Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Law
authors.forename: D P
authors.initials: DP
authors.lastname: Tieleman
authors.forename: M S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D004058:Diffusion; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D010455:Peptides / Q000737:chemistry*; D016062:Porosity; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000737:chemistry; D012680:Sensitivity and Specificity; D014867:Water / Q000737:chemistry*
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; C089692:M2 delta; D046911:Macromolecular Substances; D010455:Peptides; D011978:Receptors, Nicotinic; D014867:Water