Free energy calculations on the water-chain-assisted and the dehydration mechanisms of transmembrane ion permeation.
Free energy calculations on the water-chain-assisted and the dehydration mechanisms of transmembrane ion permeation.
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DOI：
10.1021/acs.jctc.9b00671
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发表时间：
2019-11
影响因子：
5.5
通讯作者：
Xiaoqing Guan;D. Wei;Dan Hu
中科院分区：
文献类型：
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作者：
Xiaoqing Guan;D. Wei;Dan Hu
提出了离子通过脂质膜的两种渗透机制，即水链辅助机制和脱水机制。在以往的研究中，多反应坐标和平均力势计算被用于研究这种复杂的离子跨膜过程。为了减少昂贵的计算成本，我们在最近的工作中建立了两个新的反应坐标，并对这两种渗透机理进行了研究。本研究成功地采用了我们最近工作中开发的一维自由能计算方法：首先，使用两个反应坐标进行一维伞形采样；然后，在多维相空间中沿过渡路径进行二元分割；最后，采用加权最小二乘分析方法（Welsam）进行自由能分析。基于新的反应坐标和一维自由能计算方法，系统研究了钠离子和氯离子通过不同厚度脂质双分子层的两种跨膜渗透机理。我们的研究结果表明，水链辅助机制是阳离子的主导机制，而阴离子通过厚膜的脱水机制是竞争性的，这与之前的实验结果一致。
Two permeation mechanisms, namely the water-chain-assisted mechanism and the dehydration mechanism, have been proposed for ions through lipid membranes. In previous studies, multiple reaction coordinates and potential of mean force calculations have been applied in studying such complex transmembrane processes of ions. To reduce the expensive computational cost, we develop two new reaction coordinates in our recent work and this work to study the two permeation mechanisms. An intrinsically one-dimensional free energy calculation method developed in our recent works is successfully employed in these studies: First, one-dimensional umbrella samplings are performed using the two reaction coordinates; Then, bin-segmentations are performed along the transition paths in multi-dimensional phase spaces; Finally, the weighted least square analysis method (Welsam) is used for free energy analysis. Based on the new reaction coordinates and the one-dimensional free energy calculation method, we systematically study the two transmembrane permeation mechanisms of sodium ion and chloride ion through lipid bilayers with different thicknesses. Our results suggest that the water-chain-assisted mechanism is dominant for cations, whereas the dehydration mechanism is competitive for anions through thick membranes, which is consistent with previous experimental results.