COMPUTATIONAL STUDIES OF ION CHANNELS

离子通道的计算研究

• 批准号: 6490163
• 负责人: BENOIT ROUX
• 金额: $ 30.51万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6490163
• 关键词: bioengineering /biomedical engineering; biophysics; chemical models; computer program /software; computer simulation; computer system design /evaluation; ion transport; ionic bond; membrane channels; membrane permeability; model design /development; molecular biology information system; molecular dynamics; neurotoxins; potassium; potassium channel; structural biology; technology /technique development; thermodynamics

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.

离子通道是高度特异性的膜扫描蛋白结构，促进和控制离子在整个细胞膜中的传递，我们的目标是更深入地深入了解某些重要离子通道的结构和功能，并为理解基础的基础，以了解基本的显微镜原理使用计算方法。我们将研究KCSA通道的几个方面，这是钾离子唯一选择性的通道选择性，以在原子分辨率下确定三维（3D）结构。此外，我们将构建和完善重要K通道的3D模型。使用其同源性T9是已知的KCSA，并使用来自突变循环的数据生成与通道模型相关的毒素的模型。这些建模项目相互关联，例如，毒素/通道复合物有助于验证通道模型。最后，我们将建立离子渗透描述的显微镜有效性（Brownian Dynamics，Nernst-Planck，Poisson-Nernst-Planck，Poisson-Boltzmann和动力学速率模型）在与分子动力学刺激方面有关，并阐明了电气对电荷特异性的电层学的重要性。用于模拟离子渗透的新软件将开发并自由分发用于研究和教育。我们使用这些计算的目标是补充（有时有限的）信息，这些信息目前可从实验中获得，最终在我们对离子渠道的理解中进步。此外，计算用于表征各种微观因素，这些因子无法轻易实验，但对于理解通道功能的分子决定因素至关重要。