Molecular Structure and Function, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Biochem Cell Biol. 2010 Apr;88(2):269-90. doi: 10.1139/o09-169.
Protein disorder is abundant in proteomes throughout all kingdoms of life and serves many biologically important roles. Disordered states of proteins are challenging to study experimentally due to their structural heterogeneity and tendency to aggregate. Computer simulations, which are not impeded by these properties, have recently emerged as a useful tool to characterize the conformational ensembles of intrinsically disordered proteins. In this review, we provide a survey of computational studies of protein disorder with an emphasis on the interdisciplinary nature of these studies. The application of simulation techniques to the study of disordered states is described in the context of experimental and bioinformatics approaches. Experimental data can be incorporated into simulations, and simulations can provide predictions for experiment. In this way, simulations have been integrated into the existing methodologies for the study of disordered state ensembles. We provide recent examples of simulations of disordered states from the literature and our own work. Throughout the review, we emphasize important predictions and biophysical understanding made possible through the use of simulations. This review is intended as both an overview and a guide for structural biologists and theoretical biophysicists seeking accurate, atomic-level descriptions of disordered state ensembles.
蛋白质无序状态在所有生命领域的蛋白质组中都很丰富，并且具有许多重要的生物学功能。由于蛋白质的结构异质性和聚集倾向，无序状态的蛋白质很难进行实验研究。计算机模拟技术最近作为一种有用的工具出现，可用于描述固有无序蛋白质的构象集合。在这篇综述中，我们对蛋白质无序状态的计算研究进行了调查，重点介绍了这些研究的跨学科性质。模拟技术在无序状态研究中的应用是在实验和生物信息学方法的背景下描述的。可以将实验数据纳入模拟中，并且模拟可以为实验提供预测。通过这种方式，模拟已被整合到用于研究无序状态集合的现有方法中。我们提供了文献和我们自己工作中无序状态模拟的最新示例。在整篇综述中，我们强调了通过使用模拟技术可以实现的重要预测和生物物理理解。本综述旨在为寻求无序状态集合的准确原子级描述的结构生物学家和理论生物物理学家提供概述和指南。
