COMPUTATIONAL STUDIES OF ION CHANNELS

离子通道是一种高度特异的膜扫描蛋白质结构，它促进和控制离子通过细胞膜，我们的目标是更深入地了解一些重要的离子通道的结构和功能，并为使用计算方法理解控制离子渗透的基本微观原理奠定基础。我们将研究KCSA通道的几个方面，KCSA通道是唯一一个选择钾离子的通道，其三维(3D)结构是在原子分辨率下确定的。此外，我们还将构建和完善重要K通道的3D模型。使用它们的同源性t9已知的KCSA，并使用突变循环的数据生成与通道模型相关的抑制毒素模型。这些建模项目是相互关联的，例如，毒素/通道复合体有助于验证通道模型。最后，我们将建立描述离子渗透(布朗动力学、Nernst-Planck、Poisson-Nernst-Planck、Poisson-Boltzmann和动力学速率模型)与分子动力学刺激相关的微观有效性范围，并阐明静电学对孔蛋白电荷专一性的重要性。将开发用于模拟离子渗透的新软件，并免费分发用于研究和教育。我们进行这些计算的目的是补充目前从实验中获得的(有时是有限的)信息，并最终补充我们对离子通道的理解方面的进展。此外，这些计算还被用来表征各种微观因素，这些因素不容易通过实验获得，但对于理解通道功能的分子决定因素是必不可少的。

Ion channels are highly specific membrane-scanning protein structures which facilitate and control the passage of ions across the cell membrane, our goal is to gain deeper insight into the structure and function of some important ion channels and lay the foundations for an understanding of the fundamental microscopic principles governing ion permeation using computational methods. We will study several aspects of the KcsA channel, the only channel selective for potassium ions for which the three-dimensional (3d) structure was determined at atomic resolution. In addition, we will construct and refine 3d models of important K-channels. Using their homology t9 the known KcsA , and generate models of inhibiting toxins associated with the channel models using data from mutant cycles. These modeling projects are inter-related, e.g., the toxin/channel complexes are helpful for validating the channel models. Lastly, we will establish the range of microscopic validity of descriptions of ion permeation (Brownian dynamics, Nernst-Planck, Poisson-Nernst-Planck, Poisson- Boltzmann, and kinetic rate models) in relation to molecular dynamics stimulations and elucidate the importance of electrostatics on the charge specificity of porins. New software for simulating ion permeation will be developed and freely distributed for research and education. Our goal with these computations is to complement the (sometimes limited) information that is currently available from experiments and, ultimately, progress in our understanding of ion channels. In addition, the calculations are used to characterize various microscopic factors which cannot easily be accessed experimentally, but are essential for understanding the molecular determinants of channel function.