A Hierarchy of Models of the Open Channel

该项目将深入了解离子通道中离子传导的分子机制。这项工作将是理论性的，并将试图模拟渗透离子在电化学梯度的驱动下沿着离子通道的隧道行进时与不同侧基的相互作用。由于生物离子通道的详细三维结构尚未确定，研究人员建议通过使用具有已知三维结构的充分研究的离子通道（gramicidin a）来解决这个问题。提出的研究重点是利用层次模型逐步重建渗透至ms时间范围。建模尝试将包括：(i)分子动力学模拟，生成渗透离子的路径和能量分布；（ii）利用分子动力学模拟的结果计算朗之万方程；（iii）利用更新过程理论，预测可测量的参数，如占用概率、电流/电压关系。开放通道噪声和其他可测量的单离子通道现象。(i)和（ii）的目标是评估当离子占据通道时通道的结构是如何变化的，（iii）的目标是预测单个离子通道的性质，如传输速率、选择性和开放通道噪声。

This project will provide insight into the molecular mechanism of ionic conduction in ion channels. The work will be theoretical and will attempt to model the interaction of the permeating ion with different side groups while it travels along the tunnel of the ion channel, driven by an electrochemical gradient. Since the detailed three-dimensional structure of biological ion channels has not yet been determined, the investigator proposes to tackle this problem by using a well studied ion channel with a known 3-D structure (gramicidin A). The proposed studies focus on utilizing a hierarchy of models that will gradually reconstruct permeation up to the ms time range. The modelling attempts will cover: (i) molecular dynamics simulations to generate the paths and energy profiles for the permeating ions, (ii) computation of the Langevin equation using the results of the molecular dynamics simulation, and (iii) to use the theory of renewal processes, to predict measurable parameters such as the probability of occupancy, current/voltage relationships, open channel noise and other measurable single ion channel phenomena. The goal of (i) and (ii) is to evaluate how the structure of the tunnel of a channel changes when it is occupied by ions, and the goal of (iii) is to predict the properties of single ion channels like the rate of transport, selectivity and open channel noise.