Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Jülich, Germany.
Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Jülich, Germany; AICES Graduate School, RWTH Aachen University, Aachen, Germany.
Prog Mol Biol Transl Sci. 2021;183:135-185. doi: 10.1016/bs.pmbts.2021.06.003. Epub 2021 Jul 29.
Intrinsically disordered proteins (IDPs) lack a well-defined three-dimensional structure but do exhibit some dynamical and structural ordering. The structural plasticity of IDPs indicates that entropy-driven motions are crucial for their function. Many IDPs undergo function-related disorder-to-order transitions upon by their interaction with specific binding partners. Approaches that are based on both experimental and theoretical tools enable the biophysical characterization of IDPs. Molecular simulations provide insights into IDP structural ensembles and disorder-to-order transition mechanisms. However, such studies depend strongly on the chosen force field parameters and simulation techniques. In this chapter, we provide an overview of IDP characteristics, review all-atom force fields recently developed for IDPs, and present molecular dynamics-based simulation methods that allow IDP ensemble generation as well as the characterization of disorder-to-order transitions. In particular, we introduce metadynamics, replica exchange molecular dynamics simulations, and also kinetic models resulting from Markov State modeling, and provide various examples for the successful application of these simulation methods to IDPs.
无规卷曲蛋白质（IDPs）缺乏明确的三维结构，但确实表现出一些动态和结构有序性。IDPs 的结构可塑性表明，熵驱动的运动对其功能至关重要。许多 IDPs 在与特定结合伴侣相互作用时会发生与功能相关的无序到有序的转变。基于实验和理论工具的方法能够对 IDPs 进行生物物理特性分析。分子模拟为 IDP 结构集合和无序到有序转变机制提供了深入了解。然而，这些研究强烈依赖于所选力场参数和模拟技术。在本章中，我们提供了 IDP 特性的概述，回顾了最近为 IDPs 开发的全原子力场，并介绍了基于分子动力学的模拟方法，这些方法允许生成 IDP 集合以及无序到有序转变的特性分析。特别是，我们介绍了元动力学、复制交换分子动力学模拟，以及来自马尔可夫状态建模的动力学模型，并提供了这些模拟方法成功应用于 IDPs 的各种实例。
