Tepper Harald L, Voth Gregory A
FOM Institute for Atomic and Molecular Physics, AMOLF, Kruislaan 407, 1098 SJ Amsterdam, The Netherlands.
J Phys Chem B. 2006 Oct 26;110(42):21327-37. doi: 10.1021/jp064192h.
Multistate empirical valence bond and classical molecular dynamics simulations were used to explore mechanisms for passive ion leakage through a dimyristoyl phosphatidylcholine lipid bilayer. In accordance with a previous study on proton leakage (Biophys. J. 2005, 88, 3095), it was found that the permeation mechanism must be a highly concerted one, in which ion, solvent, and membrane coordinates are coupled. The presence of the ion itself significantly alters the response of those coordinates, suggesting that simulations of transmembrane water structures without explicit inclusion of the ionic solute are insufficient for elucidating transition mechanisms. The properties of H(+), Na(+), OH(-), and bare water molecules in the membrane interior were compared, both by biased sampling techniques and by constructing complete and unbiased transition paths. It was found that the anomalous difference in leakage rates between protons and other cations can be largely explained by charge delocalization effects rather than the usual kinetic picture (Grotthuss hopping of the proton). Permeability differences between anions and cations through phosphatidylcholine bilayers are correlated with suppression of favorable membrane breathing modes by cations.
利用多态经验价键和经典分子动力学模拟来探究离子通过二肉豆蔻酰磷脂酰胆碱脂质双层被动泄漏的机制。与之前关于质子泄漏的研究（《生物物理杂志》，2005年，88卷，3095页）一致，研究发现渗透机制必定是一种高度协同的机制，其中离子、溶剂和膜坐标相互耦合。离子本身的存在显著改变了这些坐标的响应，这表明在不明确包含离子溶质的情况下模拟跨膜水结构不足以阐明转变机制。通过有偏采样技术以及构建完整且无偏的转变路径，比较了膜内部H⁺、Na⁺、OH⁻和裸水分子的性质。研究发现，质子与其他阳离子之间泄漏速率的异常差异在很大程度上可以由电荷离域效应来解释，而不是通常的动力学图景（质子的Grotthuss跳跃）。阴离子和阳离子通过磷脂酰胆碱双层的渗透率差异与阳离子对有利膜呼吸模式的抑制相关。
