A permeation theory for single-file ion channels: One- and two-step models
A permeation theory for single-file ion channels: One- and two-step models
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DOI：
10.1063/1.3580562
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发表时间：
2011-04-28
影响因子：
4.4
通讯作者：
Nelson, Peter Hugo
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文献类型：
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作者：
Nelson, Peter Hugo
需要多少步骤来模拟离子通道的渗透？本文首次将一步和两步渗透模型与实验和MD模拟进行了比较。在最近的MD模拟中，观察到的渗透机制被鉴定为类似于具有一个电压依赖性速率决定步骤的Hodgkin和Keynes敲入机制[詹森等人，PNAS 107，5833（2010）]。这些先前公布的模拟数据拟合到一步敲模型，成功地解释了在模拟中观察到的高度非欧姆的电流-电压曲线。然而，这些预测（以及它们所基于的模拟）并不代表真实的沟道行为，其在低电压下通常是欧姆的。首次将两步缔合/解离（A/D）模型与实验进行了比较。这两个参数的模型被证明是非常一致的，与先前公布的渗透实验通过MaxiK钾通道在很宽的范围内的浓度和正电压。A/D模型也提供了一个一阶解释通过振动钾通道的渗透，但它不能解释实验观察到的不对称性。为了解决这个问题，一个新的非对称的A/D模型的变体开发使用本理论框架。它包括第三参数，其表示对应于通道的三重占据状态n的“渗透坐标”（分数电势能）的值。这种不对称的A/D模型适合于在生理浓度下通过Shaker钾通道的已发表的渗透数据，并且它成功地预测了仅基于对正电压数据（表现为线性）的拟合的负电流-电压数据（包括向超欧姆行为的过渡）的定性变化。的A/D模型似乎是定性一致的一大组已发表的MD模拟，但尚未进行定量比较。A/D模型对基本步骤和通道占用率如何随浓度和电压变化进行预测。此外，所提出的理论框架提出了一种新的方法来绘制模拟系统的能量，使用一维渗透坐标，使用电势能作为通过渗透机制的净分数进展的度量。这种方法有可能首次提供原子模拟和渗透实验之间的定量联系。(C)2011年美国物理学会。[doi：10.1063/1.3580562]
How many steps are required to model permeation through ion channels? This question is investigated by comparing one-and two-step models of permeation with experiment and MD simulation for the first time. In recent MD simulations, the observed permeation mechanism was identified as resembling a Hodgkin and Keynes knock-on mechanism with one voltage-dependent rate-determining step [Jensen et al., PNAS 107, 5833 (2010)]. These previously published simulation data are fitted to a one-step knock-on model that successfully explains the highly non-Ohmic current-voltage curve observed in the simulation. However, these predictions (and the simulations upon which they are based) are not representative of real channel behavior, which is typically Ohmic at low voltages. A two-step association/dissociation (A/D) model is then compared with experiment for the first time. This two-parameter model is shown to be remarkably consistent with previously published permeation experiments through the MaxiK potassium channel over a wide range of concentrations and positive voltages. The A/D model also provides a first-order explanation of permeation through the Shaker potassium channel, but it does not explain the asymmetry observed experimentally. To address this, a new asymmetric variant of the A/D model is developed using the present theoretical framework. It includes a third parameter that represents the value of the "permeation coordinate" (fractional electric potential energy) corresponding to the triply occupied state n of the channel. This asymmetric A/D model is fitted to published permeation data through the Shaker potassium channel at physiological concentrations, and it successfully predicts qualitative changes in the negative current-voltage data (including a transition to super-Ohmic behavior) based solely on a fit to positive-voltage data (that appear linear). The A/D model appears to be qualitatively consistent with a large group of published MD simulations, but no quantitative comparison has yet been made. The A/D model makes a network of predictions for how the elementary steps and the channel occupancy vary with both concentration and voltage. In addition, the proposed theoretical framework suggests a new way of plotting the energetics of the simulated system using a one-dimensional permeation coordinate that uses electric potential energy as a metric for the net fractional progress through the permeation mechanism. This approach has the potential to provide a quantitative connection between atomistic simulations and permeation experiments for the first time. (C) 2011 American Institute of Physics. [doi:10.1063/1.3580562]