A semi-microscopic Monte Carlo study of permeation energetics in a gramicidin-like channel: the origin of cation selectivity.
A semi-microscopic Monte Carlo study of permeation energetics in a gramicidin-like channel: the origin of cation selectivity.
复制标题
类短杆菌肽通道中渗透能量学的半显微蒙特卡罗研究：阳离子选择性的起源。
DOI：
10.1016/s0006-3495(96)79554-1
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发表时间：
1996
影响因子：
3.4
通讯作者：
Jordan,PC
中科院分区：
文献类型：
--
作者：
Dorman,V;Partenskii,MB;Jordan,PC
采用蒙特卡罗模拟方法研究了类革兰霉素通道成形器对离子自由能垒的影响。该模型明确地描述了离子、水偶极子和肽羰基；其余的自由度，散装电解质，非极性脂质和肽区，和电子（高频）介电常数，在连续的条件下处理。通道水和肽COs的贡献分别和共同进行了研究。我们发现，如果限制在它们的原始取向上，COs显著增加了阳离子渗透自由能；无论是否有水存在，CO重定向对离子-CO相互作用降低阳离子自由能垒至关重要；类钾、类铷和类铯阳离子的易位自由能谱没有宽的势垒；脂质结合肽与阴离子的相互作用比与阳离子的相互作用更有效；阴离子易位自由能谱表现出明确的最大值。利用实验数据估计离子和水从散装电解质到非极性介质（连续介质脂质）的转移自由能，我们发现了合理的离子渗透分布；阳离子结合并渗透，而阴离子不能进入通道。阳离子选择性产生的原因是，对于大小和电荷相同的离子，阴离子与水合水的结合更强。
The influence of a gramicidin-like channel former on ion free energy barriers is studied using Monte Carlo simulation. The model explicitly describes the ion, the water dipoles, and the peptide carbonyls; the remaining degrees of freedom, bulk electrolyte, non-polar lipid and peptide regions, and electronic (high frequency) permittivity, are treated in continuum terms. Contributions of the channel waters and peptide COs are studied both separately and collectively. We found that if constrained to their original orientations, the COs substantially increase the cationic permeation free energy; with or without water present, CO reorientation is crucial for ion-CO interaction to lower cation free energy barriers; the translocation free energy profiles for potassium-, rubidium-, and cesium-like cations exhibit no broad barriers; the lipid-bound peptide interacts more effectively with anions than cations; anionic translocation free energy profiles exhibit well defined maxima. Using experimental data to estimate transfer free energies of ions and water from bulk electrolyte to a non-polar dielectric (continuum lipid), we found reasonable ion permeation profiles; cations bind and permeate, whereas anions cannot enter the channel. Cation selectivity arises because, for ions of the same size and charge, anions bind hydration water more strongly.