Two-Dimensional Replica-Exchange Method for Predicting Protein-Ligand Binding Structures
Two-Dimensional Replica-Exchange Method for Predicting Protein-Ligand Binding Structures
复制标题
DOI：
10.1002/jcc.23427
复制
发表时间：
2013-11-15
影响因子：
3
通讯作者：
Okamoto, Yuko
中科院分区：
文献类型：
--
作者：
Kokubo, Hironori;Tanaka, Toshimasa;Okamoto, Yuko
我们发展了一种二维复制交换方法来预测蛋白质-配体结合结构。第一维是沿着反应坐标的伞形采样，反应坐标是蛋白质结合口袋和配体之间的距离。第二个维度是溶质回火，其中配体与蛋白质和水之间的相互作用减弱。第二维的引入使配体更容易遵循伞势，并增强结合事件，这将提高采样效率。作为测试案例，我们将我们的方法应用于两个蛋白质-配体复合物系统（MDM 2和HSP 90-alpha）。从蛋白质和配体在每个系统中彼此远离的构型开始，我们的方法预测配体结合结构，与来自蛋白质数据库的实验数据非常一致，并且比我们以前开发的复制交换伞采样方法更快地提高了采样效率。(c)2013 Wiley Periodicals，Inc.
We have developed a two-dimensional replica-exchange method for the prediction of protein-ligand binding structures. The first dimension is the umbrella sampling along the reaction coordinate, which is the distance between a protein binding pocket and a ligand. The second dimension is the solute tempering, in which the interaction between a ligand and a protein and water is weakened. The second dimension is introduced to make a ligand follow the umbrella potential more easily and enhance the binding events, which should improve the sampling efficiency. As test cases, we applied our method to two protein-ligand complex systems (MDM2 and HSP 90-alpha). Starting from the configuration in which the protein and the ligand are far away from each other in each system, our method predicted the ligand binding structures in excellent agreement with the experimental data from Protein Data Bank much faster with the improved sampling efficiency than the replica-exchange umbrella sampling method that we have previously developed. (c) 2013 Wiley Periodicals, Inc.