State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, China.
Phys Chem Chem Phys. 2021 Jan 28;23(3):2430-2437. doi: 10.1039/d0cp05484d.
Intrinsically disordered proteins (IDPs) are a group of proteins that lack well-defined structures under native conditions and carry out crucial physiological functions in various biochemical pathways. Due to the heterogeneous nature of IDPs, molecular dynamics simulations have been extensively adopted to investigate the conformational ensembles and dynamic properties of these proteins. However, their accuracy remains limited by the development of force fields and sampling algorithms. Here, we evaluated the quality of both force fields and enhanced sampling algorithms based on five short pepX peptides. Our results show that the more extended conformational ensembles sampled by the AMOEBA polarizable force field present a higher ability to reproduce experimental NMR observables than AMBER and CHARMM classical force fields. Moreover, a better agreement with experiments is achieved in the simulation of IaMD (integrated accelerated molecular dynamics) than in aMD (accelerated molecular dynamics). The results together indicate that the combination of AMOEBA force field and IaMD enhanced sampling might be a better choice for simulating IDPs. This work may provide important clues for developments and applications of force fields and enhanced sampling methods in future simulations of IDPs.
无规卷曲蛋白质（IDPs）是一组在天然条件下缺乏明确结构的蛋白质，它们在各种生化途径中发挥着至关重要的生理功能。由于 IDPs 的异质性，分子动力学模拟已被广泛用于研究这些蛋白质的构象集合和动态特性。然而，其准确性仍然受到力场和采样算法的发展限制。在这里，我们基于五个短肽 pepX 评估了力场和增强采样算法的质量。我们的结果表明，采用 AMOEBA 极化力场采样的更扩展的构象集合在重现实验 NMR 可观测性方面比 AMBER 和 CHARMM 经典力场具有更高的能力。此外，在 IaMD（集成加速分子动力学）模拟中比在 aMD（加速分子动力学）中更能与实验达成一致。这些结果共同表明，AMOEBA 力场和 IaMD 增强采样的结合可能是模拟 IDPs 的更好选择。这项工作可能为未来 IDPs 模拟中力场和增强采样方法的发展和应用提供重要线索。
