THEORETICAL CHEMICAL PHYSICS OF ION FLUX IN MEMBRANES

膜中离子流的理论化学物理

• 批准号: 3281122
• 负责人: ERIC G JAKOBSSON
• 金额: $ 10.22万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281122
• 关键词: biophysics; cations; ion transport; membrane channels; membrane permeability; membrane potentials; membrane proteins; molecular dynamics

Our large goal is to construct a physical description on the atomic scale of resolution of ion permeation through a particular polypeptide membrane channel; i.e., gramicidin A and variants formed by substitutions in various side chains. Particular specific aims in pursuit of this large goal follow: We are using liquid crystal theory and molecular simulations to understand the mechanisms of gramicidin channel formation and dissociation. We are using Brownian dynamics to study the properties of channels that permit multiple-ion occupancy, and will compare our results to data for gramicidin and potassium channels. We will use Poisson-Boltzmann theory to map electrical potentials outside the channel mouth and then use Brownian dynamics to calculate trajectories through that region in order to evaluate the resistance between the bulk of the solution and the channel mouth. We will also apply Brownian dynamics to analysis of data on blocking times of gramicidin currents by organic cations, to test the hypothesis that the blocking times for the alkali metal currents are passage times for the organic cations. We will use Brownian dynamics to compute distributions of passage times and compare them to the experimental distributions of blocking times. We will use a variant of molecular dynamics called the thermodynamic cycle-perturbation method to calculate the effect of side chain substitution on the free energy profile for ion translocation in gramicidin. We will also use time correlation therory to calculate in diffusion coefficients in the channel from these simulations. The above calculations can probably be done with only the channel, the permeant ion, and the channel waters to get the free energy difference associated with side chain substitution. We intend to proceed from there to do more elaborate molecular dynamics on a more complete system to calculate mobilities and full free energies for the ion entry, translocation, and exit processes. The methods we are developing will be applicable to understanding in detail the functioning of membrane channels of wide biological importance. This understanding, in conjunction with modern genetic techniques, may facilitate the treatment of disease involving these molecules. A second potential application lies in guiding the manufacture of synthetic ionophores, which may have transport properties tailored to effect desirable changes in the functional properties of living membranes.

我们的大目标是构建对原子的物理描述 离子通过特定介质的渗透分辨率 多肽膜通道；即甘草素A及其变异体 由不同侧链中的取代形成的。特定的特定 追求这个大目标的目标如下：我们正在使用液体 晶体理论和分子模拟来理解 革兰尼丁通道的形成和解离机制。我们 正在使用布朗动力学来研究渠道的性质 允许多离子占用，并将比较我们的结果 到甘利欣和钾通道的数据。我们将使用 泊松-玻尔兹曼理论映射外的电势 然后用布朗动力学方法进行计算 通过该区域的轨迹以评估 溶液的主体和通道之间的阻力 嘴。我们还将把布朗动力学应用到数据分析中 论有机阳离子对革兰尼丁电流的阻断时间 检验碱金属的封闭时间假设 电流是有机阳离子的通过时间。我们将使用 布朗动力学用于计算通过时间分布和 将它们与阻塞时间的实验分布进行比较。 我们将使用分子动力学的一种变体，称为 计算热力循环效应的循环摄动法 侧链取代对离子自由能分布的影响 Granicidin中的易位。我们还将使用时间相关性 用于计算通道中扩散系数的理论 这些模拟。上述计算很可能是可以完成的 只有海峡、永恒河和海峡的水 得到与侧链相关的自由能差 换人。我们打算从那里开始做更多的事情 在一个更完整的系统上详细阐述分子动力学 计算离子进入时的迁移率和全自由能， 移位和退出进程。我们正在开发的方法 将适用于详细了解 膜通道具有广泛的生物学意义。这 理解，结合现代基因技术， 可能有助于涉及这些分子的疾病的治疗。 第二个潜在的应用在于指导制造 可能具有传输特性的合成电离团 量身定做，以实现所需的功能属性更改 活的膜。