Ab initio folding of proteins with all-atom discrete molecular dynamics.-猫眼课题宝

DOI：

10.1016/j.str.2008.03.013

发表时间：

2008-07

期刊：

Structure (London, England : 1993)

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Ding F;Tsao D;Nie H;Dokholyan NV

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533517/?report=classic

离散分子动力学（DMD）是一种用于蛋白质折叠和聚集研究的快速采样方法。到目前为止，DMD被用于结合基于结构的力场来模拟简化的蛋白质模型。在这里，我们开发了一个全原子蛋白质模型和一个可转移的力场，具有包装，溶剂化和环境依赖的氢键相互作用。使用副本交换方法，我们进行折叠模拟的六个小蛋白质（20-60个残基）具有不同的天然结构。在所有情况下，在模拟中达到原生或近原生状态。对于三个小的蛋白质，观察到多个折叠过渡和计算表征的热力学与实验定量一致。全原子DMD的预测能力突出了环境依赖的氢键相互作用在蛋白质折叠建模中的重要性。该方法可用于蛋白质和蛋白质-蛋白质复合物构象空间的精确快速采样，并可应用于蛋白质工程和蛋白质-蛋白质相互作用的设计。

Discrete molecular dynamics (DMD) is a rapid sampling method used in protein folding and aggregation studies. Until now, DMD was used to perform simulations of simplified protein models in conjunction with structure-based force fields. Here, we develop an all-atom protein model and a transferable force field featuring packing, solvation, and environment-dependent hydrogen bond interactions. Using the replica exchange method, we perform folding simulations of six small proteins (20–60 residues) with distinct native structures. In all cases, native or near-native states are reached in simulations. For three small proteins, multiple folding transitions are observed and the computationally-characterized thermodynamics are in quantitative agreement with experiments. The predictive power of all-atom DMD highlights the importance of environment-dependent hydrogen bond interactions in modeling protein folding. The developed approach can be used for accurate and rapid sampling of conformational spaces of proteins and protein-protein complexes, and applied to protein engineering and design of protein-protein interactions.