Gao Ya, Zhang Chaomin, Zhang John Z H, Mei Ye
College of Fundamental Studies, Shanghai University of Engineering Science , Shanghai 201620, China.
College of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, China.
J Chem Inf Model. 2017 Feb 27;57(2):267-274. doi: 10.1021/acs.jcim.6b00589. Epub 2017 Feb 1.
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 AMBER99SB 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, AMBER99SB-ildn exhibits reliable results that agree with experiments compared with its predecessors, the AMBER14SB, AMBER99SB, AMBER99SB-ildn, and AMBER99SB 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.
内在无序蛋白（IDP）在生命的基本生物过程中发挥着关键的生物学功能。由于IDP无序状态具有高度动态和构象异质性的特点，分子动力学模拟正成为研究IDP构象集合和动力学性质不可或缺的工具。然而，迄今为止，在用于IDP的分子动力学模拟中，关于最可靠的力场仍未达成共识。在这项工作中，通过检查其重现实验核磁共振（NMR）数据的能力，对最近提出的AMBER99SB力场在一些无序多肽和蛋白质建模中的表现进行了评估。结果表明，当包含ildn侧链校正时，与它的前身AMBER14SB、AMBER99SB、AMBER99SB-ildn和AMBER99SB力场相比，AMBER99SB-ildn表现出与实验结果相符的可靠结果，并且降低蛋白质-蛋白质相互作用的总体强度以利于蛋白质-水相互作用是这种改进背后的关键因素。
