PHYSIOLOGY OF IONIC CHANNELS--EXTENDED SIMULATIONS

描述：离子通道是相当感兴趣的蛋白质， 科学和医学上。 他们控制着各种交通工具 细胞膜，因此细胞和组织的大部分生命，在健康和 疾病 每天都有数以百计的实验室研究离子的功能 一次一个分子的通道。 一些渠道的结构是 这是已知的，在未来几年内将会有更多的人知道。 的理解 渠道，特别是了解他们的功能， 他们的结构已经落后了。 的性质的计算 现在许多实验室每天都在使用 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， 开始于大约100 nsec。 这些计算是基于直接积分的 牛顿的运动定律，与原子间的力量描述的经验 潜在功能 牛顿定律的另一种表述， 自费马或拉格朗日以来， 许多 变分原理已经用于各种系统：例如， Onsager和Machlup介绍了一个这样的宏观原理， 不可逆系统 离子通道和许多蛋白质都是这样的系统。 他们已经表明，这一原理可以应用于分子系统， 作为蛋白质，它允许在时间跨度大幅度增加， 计算. 研究人员建议使用OM操作来计算属性 离子通道。 他们将预测开放通道电流，闪烁， 噪声 他们将预测门控，特别是天然的 在安德森的实验室里详细研究了这条通道。 这样，他们希望 来了解短杆菌肽在时间尺度上的原子细节 接近生物。

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.