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THEORETICAL CHEMICAL PHYSICS OF ION FLUX IN MEMBRANES

膜中离子流的理论化学物理

基本信息

批准号：
3281119
负责人：
ERIC G JAKOBSSON
金额：
$ 4.42万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1992-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3281119
关键词：
biophysics cations ion transport membrane channels membrane permeability membrane potentials membrane proteins molecular dynamics

项目摘要

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一个物理描述的原子离子渗透通过一个特定的分辨率尺度多肽膜通道;即，短杆菌肽A及其变体由各种侧链中的取代形成。特定的具体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短杆菌肽通道形成和解离的机制。我们利用布朗动力学来研究通道的性质允许多离子占据，并将比较我们的结果短杆菌肽和钾离子通道的数据。我们将使用 Poisson-Boltzmann理论描绘了然后用布朗动力学计算通过该区域的轨迹，以评估大部分溶液和通道之间的阻力嘴里我们还将布朗动力学应用于数据分析有机阳离子阻断短杆菌肽电流的时间，测试碱金属的阻断时间电流是有机阳离子的通过时间。我们将使用布朗动力学来计算通过时间的分布，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，热力学循环微扰法计算侧链取代对离子自由能分布的影响短杆菌肽的易位。我们还将使用时间相关性理论计算在通道中的扩散系数，这些模拟。上述计算大概可以做到只有通道、渗透离子和通道沃茨得到侧链的自由能差替代。我们打算从那里着手，做更多的工作在一个更完整的系统上阐述分子动力学，计算离子进入的迁移率和全自由能，易位和退出过程。我们正在开发的方法将适用于详细了解的运作，具有广泛生物学意义的膜通道。这理解，结合现代遗传技术，可以促进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合成离子载体，其可能具有传输特性定制以实现功能特性的期望变化，活膜。