The double-helical structure of DNA results from canonical base pairing and stacking interactions. However, variations from steady-state conformations resulting from mechanical perturbations in cells have physiological relevance but their dependence on sequence remains unclear. Here, we use molecular dynamics simulations showing sequence differences result in markedly different structural motifs upon physiological twisting and stretching. We simulate overextension on different sequences of DNA ((AA)12, (AT)12, (CC)12 and (CG)12) with supercoiling densities at 200 and 50 mM salt concentrations. We find that DNA denatures in the majority of stretching simulations, surprisingly including those with over-twisted DNA. GC-rich sequences are observed to be more stable than AT-rich ones, with the specific response dependent on the base pair order. Furthermore, we find that (AT)12 forms stable periodic structures with non-canonical hydrogen bonds in some regions and non-canonical stacking in others, whereas (CG)12 forms a stacking motif of four base pairs independent of supercoiling density. Our results demonstrate that 20-30% DNA extension is sufficient for breaking B-DNA around and significantly above cellular supercoiling, and that the DNA sequence is crucial for understanding structural changes under mechanical stress. Our findings have important implications for the activities of protein machinery interacting with DNA in all cells.

中文翻译：

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在拉伸、扭转约束的 DNA 中出现序列依赖性结构基序。

DNA 的双螺旋结构是由规范碱基配对和堆积相互作用产生的。然而，细胞中机械扰动引起的稳态构象的变化具有生理相关性，但它们对序列的依赖性仍不清楚。在这里，我们使用分子动力学模拟显示序列差异导致生理扭曲和拉伸时明显不同的结构基序。我们在 200 和 50 mM 盐浓度下以超螺旋密度模拟不同 DNA 序列（(AA)12、(AT)12、(CC)12 和 (CG)12）的过度延伸。我们发现 DNA 在大多数拉伸模拟中都会变性，令人惊讶的是，其中也包括那些 DNA 过度扭曲的模拟。据观察，富含 GC 的序列比富含 AT 的序列更稳定，具体响应取决于碱基对顺序。此外，我们发现 (AT)12 在某些区域形成稳定的周期结构，具有非规范氢键，在其他区域形成非规范堆叠，而 (CG)12 形成独立于超螺旋密度的四个碱基对的堆叠基序。我们的结果表明，20-30% 的 DNA 延伸足以打破细胞超螺旋附近和显着高于细胞超螺旋的 B-DNA，并且 DNA 序列对于理解机械应力下的结构变化至关重要。我们的发现对于所有细胞中与 DNA 相互作用的蛋白质机制的活动具有重要意义。