Analytical methods for structural ensembles and dynamics of intrinsically disordered proteins.
Analytical methods for structural ensembles and dynamics of intrinsically disordered proteins.
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DOI：
10.1007/s12551-016-0234-6
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发表时间：
2016
影响因子：
--
通讯作者：
MacPhee, Cait E
中科院分区：
文献类型：
--
作者：
Schor, Marieke;Mey, Antonia S J S;MacPhee, Cait E
内部无序蛋白质，不具有明确定义的三维结构的蛋白质，构成了我们蛋白质组的很大一部分，并且在信号传导和调节中特别普遍。虽然它们的重要性已经认识到了二十年，但缺乏高分辨率的实验数据。分子动力学模拟已经达到我们目前的理解的动态结构合奏采样的本质无序蛋白质的关键。在这篇综述中，我们讨论了增强的采样模拟方法，特别是适合于表征的结构合奏，沿着的应用和局限性的例子。可以使用马尔可夫状态模型严格分析系综内的动态。我们讨论了最近的事态发展，使马尔可夫状态建模研究内在无序蛋白质的一种可行的方法。最后，我们简要地讨论了挑战和未来的方向时，应用分子动力学模拟研究内在无序蛋白质。
Intrinsically disordered proteins, proteins that do not have a well-defined three-dimensional structure, make up a significant proportion of our proteome and are particularly prevalent in signaling and regulation. Although their importance has been realized for two decades, there is a lack of high-resolution experimental data. Molecular dynamics simulations have been crucial in reaching our current understanding of the dynamical structural ensemble sampled by intrinsically disordered proteins. In this review, we discuss enhanced sampling simulation methods that are particularly suitable to characterize the structural ensemble, along with examples of applications and limitations. The dynamics within the ensemble can be rigorously analyzed using Markov state models. We discuss recent developments that make Markov state modeling a viable approach for studying intrinsically disordered proteins. Finally, we briefly discuss challenges and future directions when applying molecular dynamics simulations to study intrinsically disordered proteins.