title: Molecular simulation studies of hydrophobic gating in nanopores and ion channels.
abstract: Gating in channels and nanopores plays a key role in regulating flow of ions across membranes. Molecular simulations provide a 'computational microscope' which enables us to examine the physical nature of gating mechanisms at the level of the single channel molecule. Water enclosed within the confines of a nanoscale pore may exhibit unexpected behaviour. In particular, if the molecular surfaces lining the pore are hydrophobic this promotes de-wetting of the pore. De-wetting is observed as stochastic liquid-vapour transitions within a pore, and may lead to functional closure of a pore to the flow of ions and/or water. Such behaviour was first observed in simulations of simple model nanopores and referred to as 'hydrophobic gating'. Simulations of both the nicotinic acetylcholine receptor and of TWIK-1 potassium channels (the latter alongside experimental studies) suggest hydrophobic gating may occur in some biological ion channels. Current studies are focused on designing hydrophobic gates into biomimetic nanopores.
authors: *Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
authors: Jemma L
authors: JL
authors: Trick
authors: *Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
authors: Prafulla
authors: P
authors: Aryal
authors: †Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, U.K.
authors: Stephen J
authors: SJ
authors: Tucker
authors: *Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
authors: Mark S P
authors: MS
authors: Sansom
mesh_terms: D032701:Biomimetics; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry; D008958:Models, Molecular; D058608:Nanopores; D036103:Nanotechnology; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D007473:Ion Channels; C109137:KCNK1 protein, human; D026901:Membrane Transport Proteins; D024683:Potassium Channels, Tandem Pore Domain; D011978:Receptors, Nicotinic; D014867:Water