Peter Christine, Hummer Gerhard
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
Biophys J. 2005 Oct;89(4):2222-34. doi: 10.1529/biophysj.105.065946. Epub 2005 Jul 8.
Narrow hydrophobic regions are a common feature of biological channels, with possible roles in ion-channel gating. We study the principles that govern ion transport through narrow hydrophobic membrane pores by molecular dynamics simulation of model membranes formed of hexagonally packed carbon nanotubes. We focus on the factors that determine the energetics of ion translocation through such nonpolar nanopores and compare the resulting free-energy barriers for pores with different diameters corresponding to the gating regions in closed and open forms of potassium channels. Our model system also allows us to compare the results from molecular dynamics simulations directly to continuum electrostatics calculations. Both simulations and continuum calculations show that subnanometer wide pores pose a huge free-energy barrier for ions, but a small increase in the pore diameter to approximately 1 nm nearly eliminates that barrier. We also find that in those wider channels the ion mobility is comparable to that in the bulk phase. By calculating local electrostatic potentials, we show that the long range Coulomb interactions of ions are strongly screened in the wide water-filled channels. Whereas continuum calculations capture the overall energetics reasonably well, the local water structure, which is not accounted for in this model, leads to interesting effects such as the preference of hydrated ions to move along the pore wall rather than through the center of the pore.
狭窄的疏水区域是生物通道的一个常见特征，在离子通道门控中可能发挥作用。我们通过对由六角形排列的碳纳米管形成的模型膜进行分子动力学模拟，研究了控制离子通过狭窄疏水膜孔传输的原理。我们关注决定离子通过此类非极性纳米孔转运能量学的因素，并比较了不同直径的孔在钾通道关闭和开放形式的门控区域中产生的自由能垒。我们的模型系统还使我们能够将分子动力学模拟的结果直接与连续介质静电学计算结果进行比较。模拟和连续介质计算均表明，亚纳米宽的孔对离子构成巨大的自由能垒，但孔径小幅增加至约1nm几乎消除了该能垒。我们还发现，在那些较宽的通道中，离子迁移率与本体相中相当。通过计算局部静电势，我们表明在充满水的宽通道中，离子的长程库仑相互作用受到强烈屏蔽。虽然连续介质计算能较好地捕捉整体能量学，但该模型未考虑的局部水结构会导致有趣的效应，例如水合离子倾向于沿孔壁而非通过孔中心移动。
