Simulation-guided DNAzyme based nanomachine design for identifying single nucleotide variants
Simulation-guided DNAzyme based nanomachine design for identifying single nucleotide variants
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基于模拟引导 DNAzyme 的纳米机器设计，用于识别单核苷酸变异
DOI：
10.1016/j.snb.2020.128719
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Xie Guoming
中科院分区：
文献类型：
--
作者：
Zhang Li;Zhang Zhang;Ou Xinying;Wang Yufeng;Yang Liu;Weng Zhi;Xie Guoming
单核苷酸变异（snv）是临床和生物学上必不可少的生物标志物，匹配序列的特异性杂交是区分snv的关键。然而，相似的序列会与探针错误杂交，导致假阳性。在此，我们设计了一个基于dnazyme的纳米机器，以热力学和动力学参数为指导来识别snv。合理考虑了阻断DNAzyme内环的标准吉布斯自由能，设计了准稳定的“支点交换”反应。这些模拟使得在各种条件下区分snv的性能达到最佳。此外，我们还引入了一种DNA燃料来实现非共价DNA催化反应，通过改变DNA燃料的浓度来调节纳米机器的性能。通过这种方式，我们在区分snv的敏感性和特异性之间做出了令人满意的权衡。总的来说，该纳米机器产生的辨别因子在5 ~ 31之间，检测限为0.1%的变异等位基因也可以被识别出来。我们的工作通过硅模拟展示了一条有助于DNA纳米机器设计的途径，这对复杂DNA纳米机器和生物传感器的应用具有很大的潜力。
Single nucleotide variants (SNVs) are essential biomarkers both clinically and biologically, and the specific hybridization of matched sequences is crucial to discriminate SNVs. However, the similar sequence would hybridize to probes incorrectly and cause false positive. Herein, we designed a DNAzyme-based nanomachine guided by thermodynamic and kinetic parameters to identify SNVs. The standard Gibbs free energy of the internal loop in the blocked DNAzyme was rationally taken into consideration and a quasi-steady 'toehold exchange' reaction was designed. These simulations in silico enable an optimal performance to discriminate SNVs for various conditions. Additionally, we introduced a DNA fuel to enable non-covalent DNA catalysis reaction, which can tune the performance of nanomachine by changing the concentration of DNA fuel. In this way, we make a satisfactory trade-off between sensitivity and specificity to discriminate SNVs. Collectively, this nanomachine produced discrimination factors between 5 and 31, the detection limit of 0.1 % variant alleles can also be identified. Our work demonstrated a pathway assist to the design of DNA nanomachine through simulation in silico, which hold great potential for the application of complex DNA nanomachines and biosensors.
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影响因子：
16.6
作者：
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通讯作者：
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DOI：
10.1039/c3cc49873e
发表时间：
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期刊：
Chem Commun (Camb)
影响因子：
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作者：
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3.2
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通讯作者：
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影响因子：
12.6
作者：
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通讯作者：
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