Water and hydrophobic gates in ion channels and nanopores.
Water and hydrophobic gates in ion channels and nanopores.
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DOI：
10.1039/c8fd00013a
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发表时间：
2018-09-28
影响因子：
3.4
通讯作者：
Sansom MSP
中科院分区：
文献类型：
--
作者：
Rao S;Lynch CI;Klesse G;Oakley GE;Stansfeld PJ;Tucker SJ;Sansom MSP
水行为的模拟已被用于探测BEST 1和TMEM 175中的疏水门，这可以揭示新型仿生纳米孔中门的工程设计的重要原则。离子通道蛋白在生物膜中形成纳米孔，允许离子和水分子通过。这种孔中的疏水收缩可以形成门，即对水和离子渗透的能量屏障。离子通道中水的分子动力学模拟可用于评估疏水门是关闭的（即离子不可渗透的）还是打开的。如果存在对水渗透的能量屏障，那么门也可能是离子不可渗透的。模拟水的行为已被用来探测疏水门在两个最近报道的离子通道结构：BEST 1和TMEM 175。在这些通道中的每一个中，由疏水侧链的三个连续环形成狭窄区域，并且在这两种情况下，这种分析表明晶体结构对应于通道的闭合状态。BEST 1的计算机模拟突变也被用于探索门控收缩的疏水性变化的影响，证明用更极性的侧链取代疏水侧链导致允许水渗透的打开的门。TMEM 175通道的可能的开放状态通过疏水性门的计算机模拟膨胀进行建模，导致孔的润湿和钾离子通过通道的自由渗透。最后，初步研究表明，疏水门基序可以通过计算机从BEST 1通道移植到简单的β-桶孔模板中。总的来说，这些结果表明，模拟疏水门中水的行为可以揭示在新型仿生纳米孔中工程化门的重要设计原则。
Simulations of water behaviour have been used to probe hydrophobic gates in BEST1 and TMEM175, which can reveal important design principles for the engineering of gates in novel biomimetic nanopores. Ion channel proteins form nanopores in biological membranes which allow the passage of ions and water molecules. Hydrophobic constrictions in such pores can form gates, i.e. energetic barriers to water and ion permeation. Molecular dynamics simulations of water in ion channels may be used to assess whether a hydrophobic gate is closed (i.e. impermeable to ions) or open. If there is an energetic barrier to water permeation then it is likely that a gate will also be impermeable to ions. Simulations of water behaviour have been used to probe hydrophobic gates in two recently reported ion channel structures: BEST1 and TMEM175. In each of these channels a narrow region is formed by three consecutive rings of hydrophobic sidechains and in both cases such analysis demonstrates that the crystal structures correspond to a closed state of the channel. In silico mutations of BEST1 have also been used to explore the effect of changes in the hydrophobicity of the gating constriction, demonstrating that substitution of hydrophobic sidechains with more polar sidechains results in an open gate which allows water permeation. A possible open state of the TMEM175 channel was modelled by the in silico expansion of the hydrophobic gate resulting in the wetting of the pore and free permeation of potassium ions through the channel. Finally, a preliminary study suggests that a hydrophobic gate motif can be transplanted in silico from the BEST1 channel into a simple β-barrel pore template. Overall, these results suggest that simulations of the behaviour of water in hydrophobic gates can reveal important design principles for the engineering of gates in novel biomimetic nanopores.
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影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
16.6
作者：
Aryal, Prafulla;Abd-Wahab, Firdaus;Bucci, Giovanna;Sansom, Mark S. P.;Tucker, Stephen J.
通讯作者：
Tucker, Stephen J.
DOI：
10.1073/pnas.0711561105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Chen, Min;Khalid, Syma;Bayley, Hagan
通讯作者：
Bayley, Hagan
影响因子：
2
作者：
Beckstein, O;Sansom, MSP
通讯作者：
Sansom, MSP