Ion permeation through the α-hemolysin channel:: Theoretical studies based on Brownian dynamics and Poisson-Nernst-Plank electrodiffusion theory
Ion permeation through the α-hemolysin channel:: Theoretical studies based on Brownian dynamics and Poisson-Nernst-Plank electrodiffusion theory
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DOI：
10.1529/biophysj.104.044008
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发表时间：
2004-10-01
影响因子：
3.4
通讯作者：
Roux, B
中科院分区：
文献类型：
--
作者：
Noskov, SY;Im, W;Roux, B
识别控制离子通过生物孔传导的分子相互作用是现代电生理学最重要的目标之一。巨正则蒙特卡罗布朗动力学（GCMC/BD）和三维Poisson-Nernst-Plank（3d-PNP）电扩散算法为研究离子在宽分子孔中的渗透提供了强有力的通用方法。一系列的模拟在不同的浓度和跨膜电位的基础上，通过葡萄球菌α-溶血素通道的离子流的详细分析。位置相关的扩散系数近似的基础上的流体动力学模型。用GCMC/BD计算的通道电导比电生理测量的实验值高出10%，而3d-PNP的结果总是高出30 - 50%。这两种方法都能够捕获所有重要的静电相互作用在平衡条件下。GCMC/BD和3d-PNP再现了实验观察到的跨膜电位极性不对称电导。通道对离子传导的几何和能量影响的分离表明，这种不对称性是由孔内的永久电荷分布引起的。不对称性的主要决定因素是极性残基D127、D128和K131的三联体中的不平衡电荷。GCMC/BD或3d-PNP计算也再现了不对称离子溶液中的实验反转电位和渗透率。通道的弱阴离子选择性是由于在收缩区E111和K147之间存在盐桥。计算还再现了实验得出的依赖性的可逆电位的盐梯度的方向。这种效应的起源是由于能量势垒沿着通道轴的不对称分布，它调节了离子在不同方向上的优先通过。
Identification of the molecular interaction governing ion conduction through biological pores is one of the most important goals of modern electrophysiology. Grand canonical Monte Carlo Brownian dynamics (GCMC/BD) and three-dimensional Poisson-Nernst-Plank (3d-PNP) electrodiffusion algorithms offer powerful and general approaches to study of ion permeation through wide molecular pores. A detailed analysis of ion flows through the staphylococcal alpha-hemolysin channel based on series of simulations at different concentrations and transmembrane potentials is presented. The position-dependent diffusion coefficient is approximated on the basis of a hydrodynamic model. The channel conductance calculated by GCMC/BD is similar to10% higher than (electrophysiologically measured) experimental values, whereas results from 3d-PNP are always 30 - 50% larger. Both methods are able to capture all important electrostatic interactions in equilibrium conditions. The asymmetric conductance upon the polarity of the transmembrane potential observed experimentally is reproduced by GCMC/BD and 3d-PNP. The separation of geometrical and energetic influence of the channel on ion conduction reveals that such asymmetries arise from the permanent charge distribution inside the pore. The major determinant of the asymmetry is unbalanced charge in the triad of polar residues D127, D128, and K131. The GCMC/BD or 3d-PNP calculations reproduce also experimental reversal potentials and permeability rations in asymmetric ionic solutions. The weak anionic selectivity of the channel results from the presence of the salt bridge between E111 and K147 in the constriction zone. The calculations also reproduce the experimentally derived dependence of the reversible potential to the direction of the salt gradient. The origin of such effect arises from the asymmetrical distribution of energetic barriers along the channel axis, which modulates the preferential ion passage in different directions.