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The stability and number of nucleating interactions determine DNA hybridization rates in the absence of secondary structure
Nucleic Acids Research ( IF 14.9 ) Pub Date : 2022-07-26 , DOI: 10.1093/nar/gkac590
Sophie Hertel 1 , Richard E Spinney 1, 2 , Stephanie Y Xu 1 , Thomas E Ouldridge 3 , Richard G Morris 1, 2 , Lawrence K Lee 1, 4
Affiliation  

The kinetics of DNA hybridization are fundamental to biological processes and DNA-based technologies. However, the precise physical mechanisms that determine why different DNA sequences hybridize at different rates are not well understood. Secondary structure is one predictable factor that influences hybridization rates but is not sufficient on its own to fully explain the observed sequence-dependent variance. In this context, we measured hybridization rates of 43 different DNA sequences that are not predicted to form secondary structure and present a parsimonious physically justified model to quantify our observations. Accounting only for the combinatorics of complementary nucleating interactions and their sequence-dependent stability, the model achieves good correlation with experiment with only two free parameters. Our results indicate that greater repetition of Watson–Crick pairs increases the number of initial states able to proceed to full hybridization, with the stability of those pairings dictating the likelihood of such progression, thus providing new insight into the physical factors underpinning DNA hybridization rates.

中文翻译:

在没有二级结构的情况下,成核相互作用的稳定性和数量决定了 DNA 杂交率

DNA 杂交的动力学是生物过程和基于 DNA 的技术的基础。然而,决定不同 DNA 序列以不同速率杂交的原因的精确物理机制尚不清楚。二级结构是影响杂交率的一个可预测因素,但其本身不足以完全解释观察到的序列相关方差。在这种情况下,我们测量了 43 种不同的 DNA 序列的杂交率,这些序列预计不会形成二级结构,并提出了一个简约的物理合理模型来量化我们的观察结果。仅考虑互补成核相互作用的组合及其序列依赖稳定性,该模型与仅具有两个自由参数的实验实现了良好的相关性。
更新日期:2022-07-26
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