J Chem Theory Comput. 2020 Jan 14;16(1):700-710. doi: 10.1021/acs.jctc.9b00671. Epub 2019 Dec 3.
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 in this work to study the two permeation mechanisms. An intrinsically one-dimensional free energy calculation method developed in our recent work 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 multidimensional 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.
已有两种渗透机制（即水链辅助机制和脱水机制）被提出用于解释离子通过脂质膜的过程。在之前的研究中，已有多种反应坐标和平均力势计算被应用于研究离子的这种复杂跨膜过程。为了降低昂贵的计算成本，我们在最近的工作中开发了两种新的反应坐标，并在这项工作中研究这两种渗透机制。我们最近的工作中开发的一种固有一维自由能计算方法成功应用于这些研究中：首先，使用两个反应坐标进行一维伞形采样。然后，在多维相空间中的过渡路径上进行 bin 分段。最后，使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，我们系统地研究了钠离子和氯离子通过不同厚度脂质双层的两种跨膜渗透机制。我们的结果表明，水链辅助机制对于阳离子是主导机制，而对于阴离子，在厚膜中脱水机制是竞争机制，这与之前的实验结果一致。
