基于接触数引导的迭代多组独立分子动力学模拟实现配体-蛋白质结合与解离过程

配体的结合与解离过程在蛋白质实现其生物学功能方面非常关键，因此对这些高度动态过程的研究变得非常重要. 尽管已有实验方法可以确定蛋白质-配体复合物的三维结构，但一般仅可获得静态图片. 随着计算机算力的快速提高以及算法的优化，分子动力学模拟在探索配体的结合与解离过程方面具有诸多优势. 然而，当系统变得足够大时，分子动力学模拟的时间和空间尺度成为了巨大的挑战. 本工作提出了一种研究配体-蛋白质结合与解离的增强采样工具，它基于配体和蛋白质之间形成的接触数来引导迭代多组独立分子动力学模拟. 在腺苷酸激酶的模拟结果中，观测到配体的结合和解离过程，而使用传统分子动力学模拟在同一时间尺度下则无法实现这一过程.

Ligand Binding and Release Investigated by Contact-Guided Iterative Multiple Independent Molecular Dynamics Simulations

Binding and re-leasing ligands are critical for the bi-ological functions of many proteins, so it is impor-tant to determine these highly dy-namic processes. Although there are experimental techniques to determine the structure of a protein-ligand complex, it only provides a static picture of the system. With the rapid increase of computing power and improved algorithms, molecular dynamics (MD) simulations have diverse of superiority in probing the binding and release process. However, it remains a great challenge to overcome the time and length scales when the system becomes large. This work presents an enhanced sampling tool for ligand binding and release, which is based on iterative multiple independent MD simulations guided by contacts formed between the ligand and the protein. From the simulation results on adenylate kinase, we observe the process of ligand binding and release while the conventional MD simulations at the same time scale cannot.