Atomistic simulations of nucleosomes
Atomistic simulations of nucleosomes
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DOI：
10.1002/wcms.1139
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发表时间：
2013-07-01
影响因子：
11.4
通讯作者：
Bishop, Thomas C.
中科院分区：
文献类型：
--
作者：
Biswas, Mithun;Langowski, Joerg;Bishop, Thomas C.
近十几个核小体的全原子分子动力学（MD）模拟已经完成。总的来说，这些模拟提供了对作为染色质基本折叠单元的生物分子复合物的结构和动力学的见解。核小体包含146个碱基对的DNA，以左旋超螺旋缠绕在8个组蛋白的核心上。本文综述了基于核小体全原子MD研究的DNA、组蛋白和溶剂相互作用的研究进展。迄今为止，最长的模拟时间约为100纳秒。在这个时间尺度上，核小体是相当稳定的。DNA扭结、组蛋白尾部、溶剂和离子是高度动态的，可以很容易地使用平衡动力学方法进行研究。需要定向MD来观察大规模的结构变化。由于连续介质溶剂法无法恰当地描述离子核小体径向分布函数，因此需要明确的溶剂技术。这里回顾的原子技术被认为是必要的，以探索原子组成的近乎无限的变化，甚至存在于典型核小体八聚体中。这些新生模拟工作的持续发展将使实验学家能够在研究核小体和染色质的努力中利用合理的设计策略。(c) 2013 John Wiley & Sons, Ltd.
Nearly a dozen all-atom molecular dynamics (MD) simulations of the nucleosome have been performed. Collectively, these simulations provide insights into the structure and dynamics of the biomolecular complex that serves as the fundamental folding unit of chromatin. Nucleosomes contain 146 base pairs of DNA wrapped in a left-handed superhelix around a core of eight histones. This review provides a survey of what has been learned about DNA, histones, and solvent interactions based on all-atom MD studies of the nucleosome. The longest simulations to date are on the order of 100 nanoseconds. On this time scale, nucleosomes are quite stable. DNA kinks, the histone tails, solvent, and ions are highly dynamic and can be readily investigated using equilibrium dynamics methods. Steered MD is required to observe large-scale structural changes. The need for explicit solvent techniques is underscored by the inability of continuum solvent methods to properly describe the ion-nucleosome radial distribution functions. The atomistic techniques reviewed here are deemed necessary for exploration of the near infinite variations in atomic composition that exists even in the canonical nucleosome octamer. Continued development of these nascent simulation efforts will enable experimentalists to utilize rational design strategies in their efforts to investigate nucleosomes and chromatin. (c) 2013 John Wiley & Sons, Ltd.