Flexible selection of the solute region in replica exchange with solute tempering: Application to protein-folding simulations
Flexible selection of the solute region in replica exchange with solute tempering: Application to protein-folding simulations
复制标题
DOI：
10.1063/1.5016222
复制
发表时间：
2018-08-21
影响因子：
4.4
通讯作者：
Sugita, Yuji
中科院分区：
文献类型：
--
作者：
Kamiya, Motoshi;Sugita, Yuji
复制交换分子动力学（REMD）及其变体已被广泛用于模拟生物分子的结构和动力学。具有溶质回火的热交换（REST）是其中预定义的溶质分子的温度在复制品之间交换，而所有复制品中的溶剂温度保持恒定的方法之一。与温度REMD相比，REST大大减少了复制品的数量，而低温下的复制品通常被困在其条件下，干扰构象采样。在这里，我们介绍了一个新的计划的休息，被称为广义休息（gREST），溶质区域被定义为一个分子的一部分或一部分的势能项，如二面角能量项或Lennard-Jones能量项。我们应用这种新的方法折叠模拟的β-发夹（16个残基）和色氨酸笼（20个残基）在明确的水。在模拟中，选择蛋白质二面角能量项作为溶质区域。与传统的REST 2相比，gREST减少了在溶质温度空间中进行良好随机游走所需的副本数量，并覆盖了更宽的构象空间。考虑到普遍适用性，gREST应该成为一个有前途的工具，模拟蛋白质折叠，构象动力学，并在硅片药物设计。出版社：AIP Publishing
Replica-exchange molecular dynamics (REMD) and their variants have been widely used in simulations of the biomolecular structure and dynamics. Replica exchange with solute tempering (REST) is one of the methods where temperature of a pre-defined solute molecule is exchanged between replicas, while solvent temperatures in all the replicas are kept constant. REST greatly reduces the number of replicas compared to the temperature REMD, while replicas at low temperatures are often trapped under their conditions, interfering with the conformational sampling. Here, we introduce a new scheme of REST, referred to as generalized REST (gREST), where the solute region is defined as a part of a molecule or a part of the potential energy terms, such as the dihedral-angle energy term or Lennard-Jones energy term. We applied this new method to folding simulations of a beta-hairpin (16 residues) and a Trp-cage (20 residues) in explicit water. The protein dihedral-angle energy term is chosen as the solute region in the simulations. gREST reduces the number of replicas necessary for good random walks in the solute-temperature space and covers a wider conformational space compared to the conventional REST2. Considering the general applicability, gREST should become a promising tool for the simulations of protein folding, conformational dynamics, and an in silico drug design. Published by AIP Publishing.