Theoretical Investigations into Permeation Dynamics in Calcium- and Potassium-Selective Membrane Ion Channels

大脑中的所有电活动都由离子通道的打开和关闭来调节。因此，在分子水平上了解它们的作用机制是生物学中的一个基本问题。有许多不同类型的离子通道，每种类型都扮演着不同的角色。我们现在知道了形成离子通道的几种蛋白质的确切原子结构。利用这一新公布的信息，我们建议使用被称为同源建模的技术来建立两类重要的离子通道的精确物理模型，即钙通道和钾通道。然后，利用强大的超级计算机和我们设计的特殊计算机程序，我们建议跟踪离子在通道中的运动，并研究一些化合物或药物如何干扰通道的正常功能。具体地说，我们将试图了解用于治疗心律失常和高血压的维拉帕米是如何与钙通道相互作用的。一旦我们完全了解这些通道是如何工作的，我们就能够理解许多神经和肌肉疾病的原因，并可能找到治疗方法，例如心律失常和高血压。

All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms at a molecular level is a fundamental problem in biology. There are many different types of ion channels, each type fulfilling a different role. We now know the exact atomic structures of several types of the proteins forming ion channels. Using this newly unveiled information, we propose to build exact physical models of two important classes of ion channels, namely, the calcium channels and potassium channels, using the technique known as 'homology' modelling. Then, making use of powerful supercomputers and the special computer programs we have devised, we propose to follow the motion of ions as they move through the channel and study how some chemical compounds or drugs interfere with the normal functioning of the channel. Specifically, we will attempt to understand how verapamil, which is used to treat irregular heart beats and high blood pressure, interact with the calcium channel. Once we fully understand how these channels work, we will be able to understand the causes of, and possibly find the cures for, many neurological and muscular disorders, such as cardiac arhythmia and hypertension.