Department of Chemistry, Beijing Normal University, Beijing 100875, China.
Pitzer Center for Theoretical Chemistry, University of California, Berkeley, CA 94720, USA.
Int J Mol Sci. 2021 Mar 26;22(7):3420. doi: 10.3390/ijms22073420.
Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve the description of IDPs/IDRs but are largely in disagreement with solution experiments for the disordered states. This work considers a new direction-the connection to configurational entropy-and how it might change the nature of our understanding of protein force field development to equally well encompass globular proteins, IDRs/IDPs, and disorder-to-order transitions. We have evaluated representative pairwise and many-body protein and water force fields against experimental data on representative IDPs and IDRs, a peptide that undergoes a disorder-to-order transition, for seven globular proteins ranging in size from 130 to 266 amino acids. We find that force fields with the largest statistical fluctuations consistent with the radius of gyration and universal Lindemann values for folded states simultaneously better describe IDPs and IDRs and disorder-to-order transitions. Hence, the crux of what a force field should exhibit to well describe IDRs/IDPs is not just the balance between protein and water energetics but the balance between energetic effects and configurational entropy of folded states of globular proteins.
许多成对的加和力场被广泛应用于无规卷曲蛋白质（IDPs）和区域（IDRs），其中一些通过修改能量项来改善 IDPs/IDRs 的描述，但与无序状态的溶液实验存在很大分歧。本工作考虑了一个新的方向——与构象熵的联系，以及它如何改变我们对蛋白质力场开发的理解的性质，以便同样能够涵盖球状蛋白质、IDRs/IDPs 和无序到有序的转变。我们评估了具有代表性的成对和多体蛋白质和水力场与代表性 IDPs 和 IDRs 的实验数据的一致性，其中一个肽经历了无序到有序的转变，涉及七个大小从 130 到 266 个氨基酸的球状蛋白质。我们发现，与折叠状态的回转半径和普遍林德曼值一致的最大统计波动的力场同时更好地描述了 IDPs 和 IDRs 以及无序到有序的转变。因此，力场应该具有的良好描述 IDRs/IDPs 的关键特征不仅是蛋白质和水能量之间的平衡，还有球状蛋白质折叠状态的能量效应和构象熵之间的平衡。
