Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg 40530, Sweden.
Institut de Biologie et Chimie des Protéines, Université de Lyon I/CNRS UMR 5086, Lyon 69367, France.
Nucleic Acids Res. 2018 Feb 28;46(4):1684-1694. doi: 10.1093/nar/gkx1270.
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.
在细胞的生命周期中，DNA 的扭转限制在时间和空间上发生变化，是基因表达、DNA 修复和包装等过程的组成部分。在介观尺度上已经研究了扭转应力下 DNA 的力学行为，但对于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，它可以在全原子分子动力学模拟中精确控制 DNA 片段的总扭转。通过将这种约束应用于四个不同的 DNA 寡聚体，我们能够表明 DNA 以非常不均匀的方式对欠扭转和过扭转做出响应。某些碱基对步骤在特定的序列环境中能够吸收大部分扭转应力，而其他步骤则接近它们的松弛构象。这种不均匀性也会影响 DNA 的局部扭转模量。这些发现表明，通过局部 DNA 结构的不均匀变化，改变 DNA 上的扭转应力可以作为一种调节蛋白结合的调节剂。
