KcsA钾离子通道导通钾离子的能力受水分子影响的分子模拟研究

The Role of Water Molecules in the Process of the Ion Permeation through the KcsA Potassium Channel Studied by the Molecular Simulation Methods

钾离子通道可以选择性的导通钾离子,使其快速通过细胞膜.但是钾离子通过该通道时仍需要克服一定的能量壁垒.钾离子进入及溢出通道的难易程度可以用分子动力学模拟的方法来研究.钾离子通道对离子的高选择性及其快速导通钾离子的能力来源于其独特的离子选择性滤嘴结构.该结构决定了钾离子必须逐一通过.当一个钾离子进入滤嘴结构时,另一钾离子会随后进入.通常认为每两个钾离子中间会间隔一个水分子.那么水分子的存在和其在通道中的不同排列是否会影响钾离子通道对钾离子的导通能力?为解释这一问题,本文选取KcsA钾离子通道作为研究模型,用分子动力学模拟的方法研究了钾离子通过该通道时的难易程度与滤嘴结构内水分子排列的相关性.研究发现滤嘴结构内水分子的存在会影响其相邻钾离子的流动速度.由于水分子占据了钾离子在滤嘴内的结合位点,在一定程度上使得钾离子不易流向该位点,但同时水分子的存在又可以推动与其相邻的钾离子向前运动.因此水分子的作用具有双重性.

The potassium channel can select and conduct ions across the cell membranes. The ions passing through the channel must overcome the energetic barriers, and this process can be studied by the molecular simulation methods. The high selectivity and the conduction rate of the potassium channel rely on its specific structure called the selectivity filter, through which the ions must pass through one by one. It is widely accepted that the two ions passing through the filter are usually separated by an intervening water molecule. Can the water molecules affect the ion permeation process？ Here we studied the role of water molecules in the selectivity filter during the ion permeation process. We conducted molecular dynamics simulations and studied the ion permeation through the KcsA potassium channel under the conditions when the selectivity filter was filled with the different number of water molecules. We find that the water molecules can affect the permeation speed of the adjacent ions. The ion movement is impeded if the space is occupied by the water molecule. On the other hand, the same water molecule can facilitate the forward movement of the other ion. Therefore, water molecules can affect the ion permeation process with dual effects.