Torsional restraints on DNA change in time and space during the life of the cell and are an integral part of processes such as gene expression, DNA repair and packaging. The mechanical behavior of DNA under torsional stress has been studied on a mesoscopic scale, but little is known concerning its response at the level of individual base pairs and the effects of base pair composition. To answer this question, we have developed a geometrical restraint that can accurately control the total twist of a DNA segment during all-atom molecular dynamics simulations. By applying this restraint to four different DNA oligomers, we are able to show that DNA responds to both under- and overtwisting in a very heterogeneous manner. Certain base pair steps, in specific sequence environments, are able to absorb most of the torsional stress, leaving other steps close to their relaxed conformation. This heterogeneity also affects the local torsional modulus of DNA. These findings suggest that modifying torsional stress on DNA could act as a modulator for protein binding via the heterogeneous changes in local DNA structure.

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DNA 对扭转应力的序列依赖性响应：潜在的生物调节机制

在细胞生命过程中，DNA 的扭转约束会随着时间和空间的变化而变化，并且是基因表达、DNA 修复和包装等过程中不可或缺的一部分。DNA 在扭转应力下的机械行为已在介观尺度上进行了研究，但对其在单个碱基对水平上的响应以及碱基对组成的影响知之甚少。为了回答这个问题，我们开发了一种几何约束，可以在全原子分子动力学模拟过程中精确控制 DNA 片段的总扭曲。通过将这种限制应用于四种不同的 DNA 寡聚物，我们能够证明 DNA 以非常异质的方式对扭曲不足和过度扭曲做出反应。在特定的序列环境中，某些碱基对步骤能够吸收大部分扭转应力，使其他步骤接近其松弛构象。这种异质性也会影响 DNA 的局部扭转模量。这些发现表明，改变 DNA 上的扭转应力可以通过局部 DNA 结构的异质变化充当蛋白质结合的调节剂。