Trick Jemma L, Aryal Prafulla, Tucker Stephen J, Sansom Mark S P
*Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.
†Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, U.K.
Biochem Soc Trans. 2015 Apr;43(2):146-50. doi: 10.1042/BST20140256.
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.
通道和纳米孔中的门控在调节离子跨膜流动方面起着关键作用。分子模拟提供了一种“计算显微镜”，使我们能够在单通道分子水平上研究门控机制的物理性质。封闭在纳米级孔内的水可能会表现出意想不到的行为。特别是，如果孔内壁的分子表面是疏水的，这会促进孔的去湿。去湿表现为孔内随机的液-气转变，并可能导致孔对离子和/或水流的功能关闭。这种行为最初是在简单模型纳米孔的模拟中观察到的，被称为“疏水门控”。烟碱型乙酰胆碱受体和TWIK-1钾通道的模拟（后者与实验研究一起）表明，疏水门控可能发生在一些生物离子通道中。目前的研究集中在将疏水门控设计到仿生纳米孔中。
