title: Computational study of the transmembrane domain of the acetylcholine receptor.
abstract: The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel protein whose transmembrane domain (TM-domain) is believed to be responsible for channel gating via a hydrophobic effect. In this work, we perform molecular dynamics and Brownian dynamics simulations to investigate the effect of transmembrane potential on the conformation and water occupancy of TM-domain, and the resulting ion permeation events. The results show that the behavior of the hydrophobic gate is voltage-dependent. Large hyperpolarized membrane potential can change the conformation of TM-domain and water occupancy in this region, which may enable ion conduction. An electrostatic gating mechanism is also proposed from our simulations, which seems to play a role in addition to the well-known hydrophobic effect.
authors.affiliation: School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, WA 6009, Australia. sc3210@gmail.com
authors.forename: Chen
authors.initials: C
authors.lastname: Song
authors.forename: Ben
authors.initials: B
authors.lastname: Corry
mesh_terms: D000328:Adult; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D004560:Electricity; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008958:Models, Molecular; D016062:Porosity; D017434:Protein Structure, Tertiary; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D055672:Static Electricity; D013997:Time Factors; D014867:Water / Q000378:metabolism
chemical_list: D011950:Receptors, Cholinergic; D014867:Water; D012964:Sodium