State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, SJTU-Yale Joint Center for Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
Phys Chem Chem Phys. 2019 Oct 9;21(39):21918-21931. doi: 10.1039/c9cp03434j.
Intrinsically disordered proteins (IDPs) have received increasing attention in recent studies due to their structural heterogeneity and critical biological functions. To fully understand the structural properties and determine accurate ensembles of IDPs, molecular dynamics (MD) simulation was widely used to sample diverse conformations and reveal the structural dynamics. However, the classical state-of-the-art force fields perform well for folded proteins while being unsatisfactory for the simulations of disordered proteins reported in many previous studies. Thus, improved force fields were developed to precisely describe both folded proteins and disordered proteins. Preliminary tests show that our newly developed CHARMM36IDPSFF (C36IDPSFF) force field can well reproduce the experimental observables of several disordered proteins, but more tests on different types of proteins are needed to further evaluate the performance of C36IDPSFF. Here, we extensively simulate short peptides, disordered proteins, and fast-folding proteins as well as folded proteins, and compare the simulated results with the experimental observables. The simulation results show that C36IDPSFF could substantially reproduce the experimental observables for most of the tested proteins but some limitations are also found in the radius of gyration of large disordered proteins and the stability of fast-folding proteins. This force field will facilitate large scale studies of protein structural dynamics and functions using MD simulations.
在最近的研究中，由于其结构异质性和关键的生物学功能，无规卷曲蛋白质（IDP）受到了越来越多的关注。为了充分了解结构特性并确定 IDP 的准确集合，广泛使用分子动力学（MD）模拟来采样不同的构象并揭示结构动力学。然而，经典的最先进的力场在折叠蛋白质的模拟中表现良好，而在许多先前的研究中报道的无序蛋白质的模拟中并不令人满意。因此，开发了改进的力场来精确描述折叠蛋白质和无序蛋白质。初步测试表明，我们新开发的 CHARMM36IDPSFF（C36IDPSFF）力场可以很好地再现几个无序蛋白质的实验可观测值，但需要对不同类型的蛋白质进行更多测试，以进一步评估 C36IDPSFF 的性能。在这里，我们广泛模拟短肽、无序蛋白质、快速折叠蛋白质以及折叠蛋白质，并将模拟结果与实验可观测值进行比较。模拟结果表明，C36IDPSFF 可以很好地再现大多数测试蛋白质的实验可观测值，但在大的无序蛋白质的旋转半径和快速折叠蛋白质的稳定性方面也存在一些局限性。该力场将促进使用 MD 模拟对蛋白质结构动力学和功能进行大规模研究。
