Structural flexibility of the nucleosome core particle at atomic resolution studied by molecular dynamics simulation
Structural flexibility of the nucleosome core particle at atomic resolution studied by molecular dynamics simulation
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DOI：
10.1002/bip.20690
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发表时间：
2007-04-05
期刊：
影响因子：
2.9
通讯作者：
Zacharias, Martin
中科院分区：
文献类型：
--
作者：
Roccatano, Danilo;Barthel, Andre;Zacharias, Martin
比较显式溶剂分子动力学（MD）模拟是对一个完整的核小体核心粒子进行的，模拟是为了研究组蛋白n端尾部等可移动元件的动力学以及包装和DNA弯曲如何影响DNA的精细结构和动力学。除了尾部，组蛋白和DNA分子平均保持接近晶体起始结构，支持当前力场方法的质量。尽管存在包装应变，但与常规B-DNA相比，未观察到向非规范核酸主干构象的过渡增加。总的来说，DNA上的扭结和弯曲的模式与实验结果很接近。除了局部动力学之外，模拟还允许分析超螺旋迁移率，表明被一个超螺旋旋转分隔的DATA片段的相对迁移率有限（平均相对位移约为+/- 0.2 nm，主要沿着超螺旋轴）。组蛋白尾部相对运动超过20ns时，硬度更高。波动的主要目的是通过半超螺旋旋转（大约+/- 0.1 nm）分离的片段。在纳秒的时间尺度上，n端尾部发生了戏剧性的构象重排，向着DNA的部分和瞬时包裹状态转变，许多组蛋白尾部的变化对应于从完全溶剂暴露状态到DNA的主要和次要凹槽复合物的耦合结合和折叠事件。模拟结果表明，尾巴的快速构象变化可以在几纳秒内调节DNA的接近性。(c) 2007 Wiley期刊公司
Comparative explicit solvent molecular dynamics (MD) simulations have been performs on a complete nucleasome core particle with and without N-terminal simulations was to study the dynamics of mobile elements such as histone N-terminal tails and how packing and DNA-bending influences the fine structure and dynamics of DNA. Except for the tails, histone and DNA molecules stayed on average close to the crystallographic start structure supporting the quality of the current force field approach. Despite the packing strain, no increase of transitions to noncanonical nucleic acid backbone conformations compared to regular B-DNA was observed. The pattern of kinks and bends along the DNA remained close to the experiment overall. In addition to the local dynamics, the simulations allowed the analysis of the superhelical mobility indicating a limited relative mobility of DATA segments separated by one superhelical turn (mean relative displacement of approximately +/- 0.2 nm, mainly along the superhelical axis). An even higher rigidity was found for relative motions (distance histone tails for more than 20 ns. Main purpose of the fluctuations) of segments seperated by half a superhelical turn (approximately +/- 0.1 nm). The N-terminal tails underwent dramatic conformational rearrngements on the nanosecond time scale toward partially and transiently wrapped states around the DNA many of the histone tail changes corresponded to coupled association and folding events from fully solvent-exposed states toward complexes with the major and minor grooves of DNA. The simulations indicate that the rapid conformational changes of the tails can modulate the DNA accessibility within a few nanoseconds. (c) 2007 Wiley Periodicals, Inc.