DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization.
DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization.
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DOI：
10.1093/nar/gkv582
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发表时间：
2015-07-27
影响因子：
14.9
通讯作者：
Doye JP
中科院分区：
文献类型：
--
作者：
Schreck JS;Ouldridge TE;Romano F;Šulc P;Shaw LP;Louis AA;Doye JP
二级结构对DNA双链体形成的影响知之甚少。使用oxDNA，一个核苷酸水平的粗粒度DNA模型，我们研究发夹如何影响DNA杂交的速率和反应途径。我们比较高等人研究的实验系统。并发现与具有有限二级结构的DNA相比，3-碱基对发夹使杂交率降低2倍，4-碱基对发夹使杂交率降低10倍，这与实验非常一致。相比之下，熔化速率被加速了100和2000倍。这种令人惊讶的大加速发生是因为发夹在熔化过程中形成，并显着降低解离的自由能垒。这些结果应有助于实验者在设计序列中使用的DNA纳米技术，通过限制杂交反应速率的抑制，通过使用发夹和提供故意增加解离速率的可能性，将发夹纳入单链。
The effect of secondary structure on DNA duplex formation is poorly understood. Using oxDNA, a nucleotide level coarse-grained model of DNA, we study how hairpins influence the rate and reaction pathways of DNA hybridzation. We compare to experimental systems studied by Gao et al. and find that 3-base pair hairpins reduce the hybridization rate by a factor of 2, and 4-base pair hairpins by a factor of 10, compared to DNA with limited secondary structure, which is in good agreement with experiments. By contrast, melting rates are accelerated by factors of ∼100 and ∼2000. This surprisingly large speed-up occurs because hairpins form during the melting process, and significantly lower the free energy barrier for dissociation. These results should assist experimentalists in designing sequences to be used in DNA nanotechnology, by putting limits on the suppression of hybridization reaction rates through the use of hairpins and offering the possibility of deliberately increasing dissociation rates by incorporating hairpins into single strands.