A Hierarchy of Models of the Open Channel

该项目将提供深入了解的分子机制， 离子通道中的离子传导。 这项工作将是理论性的 并试图模拟渗透离子的相互作用 当它沿着隧道行进时， 由电化学梯度驱动的离子通道。 以来 生物离子的详细三维结构 渠道尚未确定，调查人员建议 为了解决这个问题，我们使用了一种经过充分研究的离子通道， 已知的三维结构（短杆菌肽A）。 拟议的研究重点 利用一系列模型， 重建高达ms时间范围的渗透。 建模 尝试将包括：（一）分子动力学模拟， 产生渗透离子的路径和能量分布， (ii)计算的朗之万方程使用的结果 分子动力学模拟，以及（iii）使用 更新过程，以预测可测量的参数，如 占用概率，电流/电压关系，开路 通道噪声和其它可测量的单离子通道现象。 （i）和（ii）的目标是评估 当通道被离子占据时，通道的隧道发生变化， （iii）的目标是预测单离子通道的性质 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.