Ion permeation and selectivity of OmpF porin: A theoretical study based on molecular dynamics, brownian dynamics, and continuum electrodiffusion theory
Ion permeation and selectivity of OmpF porin: A theoretical study based on molecular dynamics, brownian dynamics, and continuum electrodiffusion theory
复制标题
DOI：
10.1016/s0022-2836(02)00778-7
复制
发表时间：
2002-09-27
影响因子：
5.6
通讯作者：
Roux, B
中科院分区：
文献类型：
--
作者：
Im, W;Roux, B
三种不同的理论方法和比较，以完善我们的理解，通过通道形成的OmpF孔蛋白从大肠杆菌的离子渗透。这些方法是全原子分子动力学（MD），其中离子，溶剂和脂质的明确表示，布朗动力学（BD），其中离子的明确表示，而溶剂和脂质表示为无特征的连续介质，和泊松-能斯特-普朗克（PNP）电扩散理论，其中溶剂和局部离子浓度表示为连续介质。首先，不同的理论方法在再现的平衡平均离子密度分布在OmpF孔蛋白沐浴由1 M KCl对称盐溶液的能力进行检查。在这些条件下，PNP理论等价于非线性Poisson-Boltzmann（PB）理论。分析表明，所有这三种方法都能够捕捉到重要的离子之间的静电相互作用和电荷分布的通道，支配离子渗透和选择性的OmpF。从这三种方法得到的K+和Cl-密度分布是非常一致的彼此，这表明在刚性蛋白质和连续介质溶剂的基础上的治疗是有效的情况下的OmpF。有趣的是，BD和连续静电再现不同的左手扭曲的离子路径K+和Cl-延伸的孔的长度，这是以前在MD观察。巨正则系综中的平衡BD模拟表明，该通道对阳离子非常有吸引力，特别是在低盐浓度下。在10 mM KCl中，孔内平均有1.55 K+。值得注意的是，即使在低至1 μ M KCl的浓度下，孔内平均仍有0.17 K+。其次，用BD和PNP计算了OmpF中的非平衡离子流，并与实验数据进行了比较。用BD计算了0.2 M和1 M KCl中的沟道电导，与实验值雅阁很好。计算重现了实验上众所周知的电导-浓度关系，并且还揭示了通道电导的不对称性（在正跨膜电位下观察到更大的电导）。三个突变体（R168 A，R132 A，和K16 A）在1 M KCl的通道电导的计算表明，在通道电导的不对称性主要来自永久的电荷分布的通道，而不是孔本身的形状。最后，在10倍盐梯度（0.1：1 M KCl）中计算的反转电位为27.4（+/-1.3）mV（BD）和22.1（+/-0.6）mV（PNP），与实验值24.3 mV非常雅阁。虽然PNP的大部分结果在定性上是合理的，但计算的通道电导比BID计算的高约50%，这可能是因为缺乏一些动态离子-离子相关性。(C)2002爱思唯尔科技有限公司。保留所有权利。
Three different theoretical approaches are used and compared to refine our understanding of ion permeation through the channel formed by OmpF porin from Escherichia coli. Those approaches are all-atom molecular dynamics (MD) in which ions, solvent, and lipids are represented explicitly, Brownian dynamics (BD) in which ions are represented explicitly, while solvent and lipids are represented as featureless dielectrics, and Poisson-Nernst-Planck (PNP) electrodiffusion theory in which both solvent and local ion concentrations are represented as a continuum. First, the ability of the different theoretical approaches in reproducing the equilibrium average ion density distribution in OmpF porin bathed by a 1 M KCl symmetric salt solution is examined. Under those conditions the PNP theory is equivalent to the non-linear Poisson-Boltzmann (PB) theory. Analysis shows that all the three approaches are able to capture the important electrostatic interactions between ions and the charge distribution of the channel that govern ion permeation and selectivity in OmpF. The K+ and Cl- density distributions obtained from the three approaches are very consistent with one another, which suggests that a treatment on the basis of a rigid protein and continuum dielectric solvent is valid in the case of OmpF. Interestingly, both BD and continuum electrostatics reproduce the distinct left-handed twisted ion pathways for K+ and Cl- extending over the length of the pore which were observed previously in MD. Equilibrium BD simulations in the grand canonical ensemble indicate that the channel is very attractive for cations, particularly at low salt concentration. On an average there is 1.55 K+ inside the pore in 10 mM KCl. Remarkably, there is still 0.17 K+ on average inside the pore even at a concentration as low as 1 muM KCl. Secondly, non-equilibrium ion flow through OmpF is calculated using BD and PNP and compared with experimental data. The channel conductance in 0.2 M and 1 M KCl calculated using BD is in excellent accord with the experimental data. The calculations reproduce the experimentally well-known conductance-concentration relation and also reveal an asymmetry in the channel conductance (a larger conductance is observed under a positive transmembrane potential). Calculations of the channel conductance for three mutants (R168A, R132A, and K16A) in 1 M KCl suggest that the asymmetry in the channel conductance arises mostly from the permanent charge distribution of the channel rather than the shape of the pore itself. Lastly, the calculated reversal potential in a tenfold salt gradient (0.1:1 M KCl) is 27.4(+/-1.3) mV (BD) and 22.1(+/-0.6) mV (PNP), in excellent accord with the experimental value of 24.3 mV. Although most of the results from PNP are qualitatively reasonable, the calculated channel conductance is about 50% higher than that calculated from BID probably because of a lack of some dynamical ion-ion correlations. (C) 2002 Elsevier Science Ltd. All rights reserved.