PHYSIOLOGY OF IONIC CHANNELS--EXTENDED SIMULATIONS

描述：离子通道是人们非常感兴趣的蛋白质， 无论是科学上还是医学上。他们控制着许多类型的交通工具 细胞膜，从而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。几个渠道的结构如下 在接下来的几年里，会有更多的人知道。对…的理解 渠道，特别是在以下方面对其功能的理解 他们的结构已经落后了。分子的性质的计算 现在许多实验室每天都在使用技术来完成蛋白质 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 开始于100毫微秒左右。这些计算是基于直接积分的。 牛顿运动定律，原子间作用力由经验描述 势函数。牛顿定律的另一种表述，即变分 原理，从费马或拉格朗日起就已经知道很长时间了。许多 变分原理已经被用于各种系统：例如， Onsager和Machlup提出了一个宏观的这样的原理， 不可逆系统。离子通道和许多蛋白质就是这样的系统。 他们已经证明，这个原理可以应用于分子系统，如 作为蛋白质，它允许大量增加的时间跨度 计算。 调查人员建议使用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，特别是本地人的变种 通道在安徒生的实验室里进行了详细的研究。通过这种方式，他们希望 要了解Graicidin如何在时间尺度上以原子细节发挥作用 正在接近生物体。

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.