Amazon.com, Inc., New York, New York 10001, USA and Center for Data Science, New York University, New York, New York 10011, USA.
J Chem Phys. 2023 Sep 14;159(10). doi: 10.1063/5.0164440.
Torsional and bending deformations of DNA molecules often occur in vivo and are important for biological functions. DNA "under stress" is a conformational state, which is by far the most frequent state during DNA-protein and gene regulation. In DNA minicircles of length <100 base pairs (bp), the combined effect of torsional and bending stresses can cause local unusual conformations, with certain base pair steps often absorbing most of the stress, leaving other steps close to their relaxed conformation. To better understand the superhelical dynamics of DNA under stress, molecular simulations of 94 bp minicircles with different torsional linking numbers were interpreted using Fourier analyses and principal component analyses. Sharp localized bends of nearly 90° in the helical axis were observed, which in turn decreased fluctuations of the rotational register and helped redistribute the torsional stress into writhe, i.e., superhelical turn up to 360°. In these kinked minicircles, only two-thirds of the DNA molecule bends and writhes and the remaining segment stays close to straight and preserves a conformational flexibility typical of canonical B-DNA (bending of 39° ± 17° distributed parsimoniously across 36 bp), which was confirmed and visualized by principal component analysis. These results confirm that stressed DNA molecules are highly heterogeneous along their sequence, with segments designed to locally store and release stress so that nearby segments can stay relaxed.
DNA 分子的扭曲和弯曲变形在体内经常发生，对生物功能很重要。“受压”的 DNA 是一种构象状态，迄今为止，它是 DNA-蛋白质和基因调控过程中最常见的状态。在长度<100 个碱基对（bp）的 DNA 小环中，扭转和弯曲应力的综合作用会导致局部出现异常构象，某些碱基对步骤通常会吸收大部分应力，而其他步骤则接近其松弛构象。为了更好地理解受压 DNA 的超螺旋动力学，使用傅里叶分析和主成分分析对具有不同扭转连接数的 94 bp 小环进行了分子模拟。观察到螺旋轴上近 90°的尖锐局部弯曲，这反过来又降低了旋转记录的波动，并有助于将扭转应力重新分配到纽结中，即超螺旋旋转高达 360°。在这些扭曲的小环中，只有三分之二的 DNA 分子发生弯曲和纽结，其余部分保持接近直线，并保持典型的规范 B-DNA 的构象灵活性（弯曲 39°±17°，分布在 36 个碱基对中），这通过主成分分析得到了证实和可视化。这些结果证实，受压 DNA 分子在其序列上具有高度的异质性，其中的片段被设计用于局部存储和释放应力，以便附近的片段可以保持松弛。
