Effects of Protein-Induced Local Bending and Sequence Dependence on the Configurations of Supercoiled DNA Minicircles
Effects of Protein-Induced Local Bending and Sequence Dependence on the Configurations of Supercoiled DNA Minicircles
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DOI：
10.1021/acs.jctc.7b01090
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发表时间：
2018-04-01
影响因子：
5.5
通讯作者：
Biton, Yoav Y.
中科院分区：
文献类型：
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作者：
Biton, Yoav Y.
具有规定连接数的短环状DNA分子（DNA微环）的统计力学在很大程度上取决于DNA的机械和几何性质，已知这些性质是序列的函数。用于执行高级模拟的一般数值方案的描述与例子，揭示了序列依赖性和局部变形的影响，所造成的蛋白质结合，在一个典型的合奏的超螺旋微环的配置。使用一个现实的过程晶粒模型，其中的序列依赖的弹性，分子内的静电相互作用，并考虑到DNA分子的不可穿透性，超螺旋微环DNA的诱导弯曲作为一个参数的平衡的分歧。为了计算分子中每对位点的位点间距离概率，利用了约束DNA分子的独特Monte Carlo方案。模拟的例子表明，不仅序列本身可以发挥重要作用，使两个远程站点的接触，但也可能存在几个竞争的接触区域。结果表明，蛋白质结合引起的局部变形可以产生以滑动运动为主的全局构型变化，使两个（原本）相距较远的位点紧密靠近，这种效应的性质与序列结构有关。
The statistical mechanics of a short circularized DNA molecule, a DNA minicircle, with a prescribed linking number depends heavily on the mechanical and geometrical properties of the DNA, which are known to be functions of the sequence. A description of a general numerical scheme used for the performed advanced simulation is presented with examples that reveal the effects of sequence dependence and local deformations, caused by protein binding, on the configurations in a canonical ensemble of a supercoiled minicircle. Using a realistic course grain model in which the sequence-dependent elasticity, the intramolecular electrostatic interactions, and the impenetrability of the DNA molecule are taken into account, the bifurcation of equilibria of supercoiled minicircle DNA with the induced bending as a parameter is shown. The unique Monte Carlo scheme for constrained DNA molecules was utilized in order to calculate site-to-site distance probabilities for each pair of sites in the molecule. The simulated examples show not only that the sequence alone can play a significant role in bringing two remote sites to a contact but also the possible existence of several competing regions of contact. The results suggest that the local deformation caused by protein binding can yield a global configurational change, dominated by slithering motion, which brings two (originally) remote sites to close proximity, and that the nature of such effect is related to the sequence architecture.