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

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

作　　者：Xin-fan Hua Xin-zheng Du Zhi-yong Zhang 华信帆;杜新正;张志勇(中国科学技术大学合肥微尺度物质科学国家研究中心,生命科学与医学部,合肥230026)

机构地区：[1]National Science Center for Physical Sciences at the Microscale,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China

出　　处：《Chinese Journal of Chemical Physics》2021年第3期334-342,I0044,I0045,I0048,共12页化学物理学报（英文）

基　　金：supported by the National Natural Science Foundation of China(No.91953101);the Strategic Priority Research Program of the Chinese Academy of Science(XDB37040202);the Hefei National Science Center Pilot Project Funds,and the New Concept Medical Research Fund of USTC。

摘　　要：Binding and releasing ligands are critical for the biological functions of many proteins,so it is important to determine these highly dynamic 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.

关 键 词：Molecular dynamics simulation Enhanced sampling Binding and releasing process Adenylate kinase 

分 类 号：O629.73[理学—有机化学]