Global and local mechanical properties control endonuclease reactivity of a DNA origami nanostructure.
Global and local mechanical properties control endonuclease reactivity of a DNA origami nanostructure.
复制标题
全局和局部机械特性控制 DNA 折纸纳米结构的核酸内切酶反应性。
DOI：
10.1093/nar/gkaa080
复制
发表时间：
2020
影响因子：
14.9
通讯作者：
Carnevale,Vincenzo
中科院分区：
文献类型：
--
作者：
Suma,Antonio;Stopar,Alex;Nicholson,AllenW;Castronovo,Matteo;Carnevale,Vincenzo
我们使用粗粒度分子动力学模拟来表征DNA折纸三角形纳米结构的全局和局部力学特性。该结构呈现两个亚稳构象，由一个自由能垒隔开，在遗漏四个特定的DNA钉（缺陷）时降低了自由能垒。相反，去除8个订书钉后，只存在一个稳定的构象。亚稳性是用三个梯形亚结构的固有构象来解释的。我们计算了内切酶的局部可及性模型，预测了20个位点的反应性，与实验数据吻合良好。我们发现全局波动影响局部反应性：由于全局波动的增加，DNA钉的去除增加了距离为40 nm的位点对限制性内切酶的计算可达性。这些结果提出了变构调节DNA折纸的合理工程的有趣可能性。
We used coarse-grained molecular dynamics simulations to characterize the global and local mechanical properties of a DNA origami triangle nanostructure. The structure presents two metastable conformations separated by a free energy barrier that is lowered upon omission of four specific DNA staples (defect). In contrast, only one stable conformation is present upon removing eight staples. The metastability is explained in terms of the intrinsic conformations of the three trapezoidal substructures. We computationally modeled the local accessibility to endonucleases, to predict the reactivity of twenty sites, and found good agreement with the experimental data. We showed that global fluctuations affect local reactivity: the removal of the DNA staples increased the computed accessibility to a restriction enzyme, at sites as distant as 40 nm, due to an increase in global fluctuation. These results raise the intriguing possibility of the rational engineering of allosterically modulated DNA origami.