A computational study of nucleosomal DNA flexibility
A computational study of nucleosomal DNA flexibility
复制标题
DOI：
10.1529/biophysj.106.082099
复制
发表时间：
2006-12-01
影响因子：
3.4
通讯作者：
Onufriev, Alexey
中科院分区：
文献类型：
--
作者：
Ruscio, Jory Z.;Onufriev, Alexey
报道了核小体核心颗粒及其在溶液中游离的分离 DNA 的分子动力学模拟。这些模拟基于隐式溶剂方法，深入了解核小体 DNA 的大规模结构波动和灵活性的本质。除了先前在核小体的 X 射线结构中识别出的扭结区域之外，模拟还支持生化识别出的 DNA 扭曲区域的存在。计算的相对自由能的比较表明，相对于光滑、理想的 DNA 超螺旋构象，扭结的形成与能量成本（如果有的话）很少相关。根据 500 A 的标准持久长度，分离的核小体 DNA 比预期的 147 bp DNA 延伸要灵活得多。值得注意的是，在我们的模拟中观察到的 DNA 的显着弯曲发生在沃森-克里克键没有断裂的情况下。计算出的弯曲构象的相对稳定性对生理范围内溶液的离子强度敏感；这种敏感性表明可能进行一些实验，以进一步了解 DNA 异常灵活性的结构起源。
Molecular dynamics simulations of the nucleosome core particle and its isolated DNA free in solution are reported. The simulations are based on the implicit solvent methodology and provide insights into the nature of large-scale structural fuctuations and flexibility of the nucleosomal DNA. In addition to the kinked regions previously identified in the x-ray structure of the nucleosome, the simulations support the existence of a biochemically identified distorted region of the DNA. Comparison of computed relative free energies shows that formation of the kinks is associated with little, if any, energy cost relative to a smooth, ideal conformation of the DNA superhelix. Isolated nucleosomal DNA is found to be considerably more flexible than expected for a 147 bp stretch of DNA based on its canonical persistence length of 500 A. Notably, the significant bending of the DNA observed in our simulations occurs without breaking of Watson-Crick bonds. The computed relative stability of bent conformations is sensitive to the ionic strength of the solution in the physiological range; the sensitivity suggests possible experiments that might provide further insights into the structural origins of the unusual flexibility of the DNA.