Evaluation of the Coupled Two-Dimensional Main Chain Torsional Potential in Modeling Intrinsically Disordered Proteins
Evaluation of the Coupled Two-Dimensional Main Chain Torsional Potential in Modeling Intrinsically Disordered Proteins
复制标题
本质无序蛋白质建模中耦合二维主链扭转势的评估
DOI：
10.1021/acs.jcim.6b00589
复制
发表时间：
2017-02-01
影响因子：
5.6
通讯作者：
Mei, Ye
中科院分区：
文献类型：
--
作者：
Gao, Ya;Zhang, Chaomin;Mei, Ye
内源性无序蛋白（IDP）在生命的基本生物学过程中发挥着重要的生物学功能。由于IDPs的无序状态具有高度的动态性和构象异质性，分子动力学模拟正成为研究IDPs的构象集合和动力学性质不可或缺的工具。然而，迄今为止，对于IDPs分子动力学模拟中最可靠的力场仍然没有达成共识。在这项工作中，最近提出的AMBER 99 SB 2D力场进行评估，在建模一些无序的多肽和蛋白质，通过检查它的能力，重现实验NMR数据。结果强调，当包括ildn侧链校正时，AMBER 99 SB 2D-ildn表现出与其前辈AMBER 14 SB，AMBER 99 SB，AMBER 99 SB-ildn和AMBER 99 SB 2D力场相比与实验一致的可靠结果，并且降低蛋白质-蛋白质相互作用的整体幅度有利于蛋白质-水相互作用是改进背后的关键因素。
Intrinsically disordered proteins (IDPs) carry out crucial biological functions in essential biological processes of life. Because of the highly dynamic and conformationally heterogeneous nature of the disordered states of IDPs, molecular dynamics simulations are becoming an indispensable tool for the investigation of the conformational ensembles and dynamic properties of IDPs. Nevertheless, there is still no consensus on the most reliable force field in molecular dynamics simulations for IDPs hitherto. In this work, the recently proposed AMBER99SB2D force field is evaluated in modeling some disordered polypeptides and proteins by checking its ability to reproduce experimental NMR data. The results highlight that when the ildn side-chain corrections are included, AMBER99SB2D-ildn exhibits reliable results that agree with experiments compared with its predecessors, the AMBER14SB, AMBER99SB, AMBER99SB-ildn, and AMBER99SB2D force fields, and that decreasing the overall magnitude of protein-protein interactions in favor of protein-water interactions is a key ingredient behind the improvement.