Roux B, Prod'hom B, Karplus M
Département de physique, Université de Montréal, Canada.
Biophys J. 1995 Mar;68(3):876-92. doi: 10.1016/S0006-3495(95)80264-X.
The structural and thermodynamic factors responsible for the singly and doubly occupied saturation states of the gramicidin channel are investigated with molecular dynamics simulations and free energy perturbation methods. The relative free energy of binding of all of the five common cations Li+, Na+, K+, Rb+, and Cs+ is calculated in the singly and doubly occupied channel and in bulk water. The atomic system, which includes the gramicidin channel, a model membrane made of neutral Lennard-Jones particles and 190 explicit water molecules to form the bulk region, is similar to the one used in previous work to calculate the free energy profile of a Na+ ion along the axis of the channel. In all of the calculations, the ions are positioned in the main binding sites located near the entrances of the channel. The calculations reveal that the doubly occupied state is relatively more favorable for the larger ions. Thermodynamic decomposition is used to show that the origin of the trend observed in the calculations is due to the loss of favorable interactions between the ion and the single file water molecules inside the channel. Small ions are better solvated by the internal water molecules in the singly occupied state than in the doubly occupied state; bigger ions are solvated almost as well in both occupation states. Water-channel interactions play a role in the channel response. The observed trends are related to general thermodynamical properties of electrolyte solutions.
运用分子动力学模拟和自由能微扰方法，研究了短杆菌肽通道单占据和双占据饱和状态的结构和热力学因素。计算了Li⁺、Na⁺、K⁺、Rb⁺和Cs⁺这五种常见阳离子在单占据和双占据通道以及本体水中的相对结合自由能。原子体系包括短杆菌肽通道、由中性伦纳德 - 琼斯粒子构成的模型膜以及190个明确的水分子以形成本体区域，这与之前用于计算Na⁺离子沿通道轴的自由能分布的体系相似。在所有计算中，离子位于通道入口附近的主要结合位点。计算结果表明，双占据状态对较大离子相对更有利。通过热力学分解表明，计算中观察到的趋势源于离子与通道内单排水分子之间有利相互作用的丧失。小离子在单占据状态下比在双占据状态下更好地被内部水分子溶剂化；大离子在两种占据状态下的溶剂化程度几乎相同。水 - 通道相互作用在通道响应中起作用。观察到的趋势与电解质溶液的一般热力学性质有关。
