State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Phys Chem Chem Phys. 2021 Jun 2;23(21):12127-12136. doi: 10.1039/d1cp01385h.
Intrinsically disordered proteins (IDPs) have no fixed tertiary structure under physiological conditions and are associated with many human diseases. Because IDPs have the characteristic of possessing diverse conformations, current experimental methods cannot capture all the conformations of IDPs. However, molecular dynamics simulation can sample these atomistically diverse conformations as a valuable complement to experimental data. To accurately describe the properties of IDPs, the environment-specific precise force field (ESFF1) was successfully released to reproduce the conformer character of ordered and disordered proteins. Here, three typical IDPs and thirteen folded proteins were used to further evaluate the performance of this force field. The results indicate that the NMR observables of ESFF1 better approach experimental data than do those of ff14SB for IDPs. The sampling conformations by ESFF1 are more diverse than those of ff14SB. For folded proteins, these force fields have comparable performances for reproducing conformers. Therefore, ESFF1 can be used to reveal the model of sequence-disorder-function for IDPs.
无规卷曲蛋白质（IDPs）在生理条件下没有固定的三级结构，与许多人类疾病有关。由于 IDPs 具有具有多种构象的特征，目前的实验方法无法捕捉 IDPs 的所有构象。然而，分子动力学模拟可以作为实验数据的有价值补充来采样这些原子多样性的构象。为了准确描述 IDPs 的特性，成功发布了环境特定精确力场（ESFF1），以再现有序和无序蛋白质的构象特征。在这里，使用了三种典型的 IDPs 和十三种折叠蛋白来进一步评估该力场的性能。结果表明，ESFF1 的 NMR 观察值比 ff14SB 更接近 IDPs 的实验数据。ESFF1 的采样构象比 ff14SB 更加多样化。对于折叠蛋白，这些力场在再现构象方面具有相当的性能。因此，ESFF1 可用于揭示 IDPs 的序列无序-功能模型。
