论文标题
水调节苯甲酰胺在胰蛋白酶中的停留时间
Water regulates the residence time of Benzamidine in Trypsin
论文作者
论文摘要
配体 - 蛋白质解链的过程对于生物物理学至关重要。水是任何生物系统的重要组成部分，但其角色的许多方面仍然难以捉摸。在这里，我们使用最先进的增强采样技术模拟了苯甲酰胺与胰蛋白酶的结合，这是一个经过研究的且范式范式的配体蛋白质系统。我们使用机器学习方法来确定复杂非本地水网络的有效集体坐标。这些坐标用于执行即时概率增强的采样模拟，我们适应了这也计算配体停留时间。我们的静态和动态结果与实验非常吻合。我们发现，位于结合口袋底部的水分子的存在可以通过氢键网络将配体释放到溶液中。在更细微的尺度上，即使允许解开，另一个水分子也进一步调节出口时间。
The process of ligand-protein unbinding is crucial in biophysics. Water is an essential part of any biological system and yet, many aspects of its role remain elusive. Here, we simulate with state-of-the-art enhanced sampling techniques the binding of Benzamidine to Trypsin which is a much studied and paradigmatic ligand-protein system. We use machine learning methods to determine efficient collective coordinates for the complex non-local network of water. These coordinates are used to perform On-the-fly Probability Enhanced Sampling simulations, which we adapt to calculate also the ligand residence time. Our results, both static and dynamic, are in good agreement with experiments. We find that the presence of a water molecule located at the bottom of the binding pocket allows via a network of hydrogen bonds the ligand to be released into the solution. On a finer scale, even when unbinding is allowed, another water molecule further modulates the exit time.
