Computerstudien zur Physik von Ionenkanälen

离子通道物理的计算机研究

• 批准号: 181677067
• 负责人: Professor Dr. Paolo Carloni
• 金额: --
• 依托单位: Bereich Computational Biomedicine (IAS-5/INM-9)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/181677067?language=en
• 关键词: Computerstudien; zur; Physik; von; Ionenkan

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.

通道和孔蛋白中的离子渗透参与关键的生物过程，例如神经冲动、心脏和平滑肌收缩。为了推进我们的理解，将结构生物学家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，我们计划与在美国芝加哥进行实验的分子生物学家合作，通过计算方法研究大肠杆菌孔蛋白 NanC 的离子渗透。我们将根据可用的结构信息计算与 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，还将使用我的小组中可用的量子力学工具。后者的计算将解决有关离子力场精度的关键问题。这项工作将得到 Bob Eisenberg 及其同事开发的旨在计算离子电流的简化模型（例如流体泊松能斯特普朗克理论的密度泛函）的补充。自由能渗透曲线之间的比较将有助于理解每种方法以及通道函数本身。然后，利用理论和实验，我们将尝试将蛋白质改造为 Na+ 选择性通道。

项目成果

Ion permeation in the NanC porin from Escherichia coli: free energy calculations along pathways identified by coarse-grain simulations.

大肠杆菌 NanC 孔蛋白中的离子渗透：沿着粗粒模拟确定的路径进行自由能计算

• DOI: 10.1021/jp4081838
• 发表时间: 2013
• 期刊: The journal of physical chemistry. B
• 作者: Dreyer J;P. Strodel;E. Ippoliti;J. Finnerty;R. Eisenberg;P. Carloni
• 通讯作者: P. Carloni

Localizing the Charged Side Chains of Ion Channels within the Crowded Charge Models.

拥挤电荷模型中离子通道的带电侧链的局部化

• DOI: 10.1021/ct300768j
• 发表时间: 2013
• 期刊: Journal of chemical theory and computation
• 影响因子: 5.5
• 作者: Finnerty J. J;R. Eisenberg;P. Carloni
• 通讯作者: P. Carloni