Computerstudien zur Physik von Ionenkanälen

离子在通道和孔道中的渗透参与了神经冲动、心脏和平滑肌收缩等关键的生物学过程。为了促进我们的理解，将结构和分子生物学家与参与分子模拟的小组联系起来是至关重要的。在这里，我们计划通过计算方法，与在美国芝加哥进行实验的分子生物学家合作，研究离子对来自大肠杆菌的孔蛋白纳米颗粒的渗透。我们将基于现有的结构信息计算与Na和K离子渗透相关的自由能。我们不仅将使用基于力场的分子动力学模拟，而且还将使用我的团队中可用的量子力学工具。后一种计算将解决与离子力场精度有关的关键问题。这项工作将由Bob Eisenberg和他的同事开发的旨在计算离子电流的简化模型(例如流体的密度泛函Poisson-Nernst-Planck理论)来补充。自由能渗透剖面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.