Water Nanoconfined in a Hydrophobic Pore: MD Simulations and Water Models
Water Nanoconfined in a Hydrophobic Pore: MD Simulations and Water Models
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DOI：
10.1101/2021.07.28.453939
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
C. Lynch;Gianni Klesse;Shanlin Rao;S. Tucker;M. Sansom
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作者：
C. Lynch;Gianni Klesse;Shanlin Rao;S. Tucker;M. Sansom
生物离子通道中的水分子处于纳米受限环境中，因此表现出不同于主体水的新行为。在这里，我们研究疏水门控现象，这是一个过程，通过这个过程，如果纳米孔足够疏水和/或狭窄，它可以自发去湿，形成“汽锁”。值得注意的是，这发生在没有类固醇堵塞毛孔的情况下。利用加性力场和可极化(阿米巴)力场的分子动力学模拟，我们研究了TMEM175离子通道中的这种润湿/去湿行为。我们研究了一系列刚性固定电荷(即添加剂)和可极化水模型如何影响野生型结构和突变体中的润湿/去湿，以覆盖一系列纳米孔半径和孔衬疏水性。重要的是，我们发现刚性固定电荷水模型导致类似的润湿/去湿行为，但可极化水模型导致孔疏水门区的润湿性增加。这对纳米承压水的分子模拟具有重要意义，因为它意味着，如果我们要获得对润湿/去湿过程的详细机械见解，可能需要包括极化率。这些发现对于设计功能化的仿生纳米孔(如传感或海水淡化)以及加深我们对生物离子通道功能的机制过程的理解都是重要的。
Water molecules within biological ion channels are in a nano-confined environment and therefore exhibit novel behaviours which differ from that of bulk water. Here, we investigate the phenomenon of hydrophobic gating, the process by which a nanopore may spontaneously de-wet to form a ‘vapour lock’ if the pore is sufficiently hydrophobic and/or narrow. Notably, this occurs without steric occlusion of the pore. Using molecular dynamics simulations with both additive and polarisable (AMOEBA) force fields, we investigate this wetting/de-wetting behaviour in the TMEM175 ion channel. We examine how a range of rigid fixed-charge (i.e. additive) and polarisable water models affect wetting/de-wetting in both the wild-type structure and in mutants chosen to cover a range of nanopore radii and pore-lining hydrophobicities. Crucially, we find that the rigid fixed-charge water models lead to similar wetting/de-wetting behaviours, but that the polarisable water model resulted in an increased wettability of the hydrophobic gating region of the pore. This has significant implications for molecular simulations of nano-confined water, as it implies that polarisability may need to be included if we are to gain detailed mechanistic insights into wetting/de-wetting processes. These findings are of importance for the design of functionalised biomimetic nanopores (for e.g. sensing or desalination), as well as for furthering our understanding of the mechanistic processes underlying biological ion channel function.