PHYSIOLOGY OF IONIC CHANNELS--EXTENDED SIMULATIONS

离子通道的生理学——扩展模拟

• 批准号: 2701794
• 负责人: ROBERT S. EISENBERG
• 金额: $ 11.21万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2701794
• 关键词: computer simulation; gramicidin; membrane channels; molecular dynamics; protein structure function

DESCRIPTION: Ionic channels are proteins of considerable interest, scientifically and medically. They control many types of transport across cell membranes and thus much of the life of cells and tissues, in health and disease. Every day hundreds of laboratories study the function of ionic channels one molecule at a time. The structures of a few channels are known, and more will be known in the next few years. The understanding of channels, in particular, the understanding of their function in terms of their structure, has lagged behind. Calculations of the properties of proteins are done now in many laboratories every day using techniques of molecular dynamics. But these calculations are severely limited in time span, unable to reach the biological time scale of channel activity which starts around 100 nsec. These calculations are based on direct integration of Newton's laws of motions, with interatomic forces described by empirical potential functions. Another formulation of Newton's laws, as variational principles, has been known for a long time, since Fermat or Lagrange. Many variational principles have been used for a variety of systems: e.g., Onsager & Machlup introduced one such principle for macroscopic, irreversible systems. Ionic channels and many proteins are such systems. They have shown that this principle can be applied to molecular systems such as proteins and that it allows a large increase in the time span of calculation. The investigators propose to use the OM action to calculate the properties of ionic channels. They will predict open channel currents, flickering, and noise. They will predict gating, particularly of variants of the native channel studied in detail in Andersen's laboratory. In this way, they hope to learn how gramicidin functions in atomic detail on a time scale approaching the biological.

描述：离子通道是人们非常感兴趣的蛋白质， 从科学和医学上来说。 他们控制着多种类型的交通 细胞膜以及细胞和组织的大部分生命，在健康和 疾病。 每天都有数百个实验室研究离子的功能 一次引导一个分子。 几个通道的结构是 已知的，并且在未来几年内将会有更多的已知。 的理解 渠道，特别是对其功能的理解 他们的结构，已经落后。 属性的计算 现在许多实验室每天都使用以下技术来制备蛋白质 分子动力学。 但这些计算在时间上受到严重限制 跨度，无法达到通道活动的生物时间尺度 大约 100 纳秒开始。 这些计算基于直接积分 牛顿运动定律，用经验描述的原子间力 潜在的功能。 牛顿定律的另一种表述是变分法 自费马或拉格朗日以来，原理早已为人所知。 许多 变分原理已用于各种系统：例如， Onsager & Machlup 引入了这样一种宏观原理， 不可逆系统。 离子通道和许多蛋白质都是这样的系统。 他们证明这一原理可以应用于分子系统，例如 作为蛋白质，它可以大大增加 计算。 研究人员建议使用 OM 操作来计算属性 离子通道。 他们将预测明渠电流、闪烁和 噪音。 他们将预测门控，特别是本地变体的门控 安徒生实验室对通道进行了详细研究。 通过这种方式，他们希望 了解短杆菌肽如何在时间尺度上以原子细节发挥作用 接近生物。