Molecular simulation studies of hydrophobic gating in nanopores and ion channels

Biochem Soc Trans. 2015 Apr;43(2):146-50. doi: 10.1042/BST20140256.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomimetics*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Computer Simulation
  • Hydrophobic and Hydrophilic Interactions
  • Ion Channel Gating*
  • Ion Channels / chemistry*
  • Ion Channels / metabolism
  • Membrane Transport Proteins / chemistry
  • Models, Molecular
  • Nanopores*
  • Nanotechnology
  • Potassium Channels, Tandem Pore Domain / chemistry
  • Potassium Channels, Tandem Pore Domain / metabolism
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / metabolism
  • Water / chemistry

Substances

  • Ion Channels
  • KCNK1 protein, human
  • Membrane Transport Proteins
  • Potassium Channels, Tandem Pore Domain
  • Receptors, Nicotinic
  • Water