Computerstudien zur Physik von Ionenkanälen

离子在通道和孔蛋白中的渗透参与关键的生物过程，如神经冲动、心脏和平滑肌收缩。为了增进我们的理解，将结构和分子生物学家与参与分子模拟的团体联系起来至关重要。在这里，我们计划研究离子渗透通过孔蛋白NanC从E。在美国芝加哥进行实验的分子生物学家的合作下，我们将根据现有的结构信息计算与Na+和K+离子渗透相关的自由能。我们将不仅使用基于力场的分子动力学模拟，而且使用我们小组可用的量子力学工具。后者的计算将解决有关离子的力场精度的关键问题。这项工作将由Bob Eisenberg及其同事开发的旨在计算离子流的简化模型（例如流体密度泛函-泊松-能斯特-普朗克理论）进行补充。自由能渗透剖面之间的比较将导致对每种方法的理解，以及对通道功能本身的理解。然后，利用理论和实验，我们将尝试将蛋白质工程化为Na+选择性通道。

Ion permeation in channels and porins is involved in key biological processes, such as nerve impulse, cardiac and smooth muscle contraction. To advance in our understanding it is crucial to link structural and molecular biologists to groups involved in molecular simulation. Here we plan to study ion permeation through the porin NanC from E. coli by computational methods, in collaboration with molecular biologists performing experiments in Chicago, US. We will calculate the free energy associated with Na+ and K+ ion permeation based on the available structural information. We will use not only force-field based molecular dynamics simulations but also tools of quantum mechanics available in my group. The latter calculations will address key issues regarding the force field accuracy of the ions. This work will be complemented by the simplified models developed by Bob Eisenberg and coworkers aimed at calculating ion currents (e.g. Density Functional of Fluid-Poisson-Nernst-Planck theory). Comparison between free energy permeation profiles will lead to understanding of each method, and of the channel function itself. Then, using theory and experiments, we will attempt at engineering the protein to a Na+ selective channel.