Fast and Robust Strand Displacement Cascades via Systematic Design Strategies
Fast and Robust Strand Displacement Cascades via Systematic Design Strategies
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DOI：
10.4230/lipics.dna.28.1
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
T. Kennedy;Cadence Pearce;Chris Thachuk
中科院分区：
文献类型：
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作者：
T. Kennedy;Cadence Pearce;Chris Thachuk
更广泛地采用分子计算的一个障碍是实现任意化学反应网络（CRN）的困难，CRN是鲁棒的，并复制设计行为的动力学。DNA链置换（DSD）级联由于其模拟任意CRN的潜力和已知的调节其反应速率的原理而成为用于此目的的受欢迎的技术。无泄漏级联的进展表明，DSD可以任意鲁棒虚假的“泄漏”反应时，纳入系统域级冗余。稳健性的这些改进导致设计反应的较慢动力学。现有的工作已经证明了在置换过程中序列错配的引入和消除的动力学和热力学效应。我们提出了一个系统的，顺序修改策略，优化无泄漏级联的动力学，而不实际的成本，他们的鲁棒性。一个深入的案例研究探讨了这种优化的效果时，适用于一个典型的无泄漏翻译级联。能垒的热力学分析和动力学实验数据支持DSD叶栅可以是快速和鲁棒的。
A barrier to wider adoption of molecular computation is the difficulty of implementing arbitrary chemical reaction networks (CRNs) that are robust and replicate the kinetics of designed behavior. DNA Strand Displacement (DSD) cascades have been a favored technology for this purpose due to their potential to emulate arbitrary CRNs and known principles to tune their reaction rates. Progress on leakless cascades has demonstrated that DSDs can be arbitrarily robust to spurious “leak” reactions when incorporating systematic domain level redundancy. These improvements in robustness result in slower kinetics of designed reactions. Existing work has demonstrated the kinetic and thermodynamic effects of sequence mismatch introduction and elimination during displacement. We present a systematic, sequence modification strategy for optimizing the kinetics of leakless cascades without practical cost to their robustness. An in-depth case study explores the effects of this optimization when applied to a typical leakless translator cascade. Thermodynamic analysis of energy barriers and kinetic experimental data support that DSD cascades can be fast and robust.