Understanding the relationship between sequences and kinetics of DNA strand displacements

作者：Da Long, Peichen Shi, Xin Xu, Jiayi Ren, Yuqing Chen, Shihui Guo, Xinchang Wang, Xiaoyu Cao, Liulin Yang, Zhong‐Qun Tian · 发表于：Nucleic Acids Research · 年份：2024 · DOI：10.1093/nar/gkae652 · 被引用次数：23 · 研究领域：Advanced biosensing and bioanalysis techniques、DNA and Nucleic Acid Chemistry、RNA and protein synthesis mechanisms

Precisely modulating the kinetics of toehold-mediated DNA strand displacements (TMSD) is essential for its application in DNA nanotechnology. The sequence in the toehold region significantly influences the kinetics of TMSD. However, due to the large sample space resulting from various arrangements of base sequences and the resulted complex secondary structures, such a correlation is not intuitive. Herein, machine learning was employed to reveal the relationship between the kinetics of TMSD and the toehold sequence as well as the correlated secondary structure of invader strands. Key factors that influence the rate constant of TMSD were identified, such as the number of free hydrogen bonding sites in the invader, the number of free bases in the toehold, and the number of hydrogen bonds in intermediates. Moreover, a predictive model was constructed, which successfully achieved semi-quantitative prediction of rate constants of TMSD even with subtle distinctions in toehold sequence.