Fast and Robust Strand Displacement Cascades via Systematic Design Strategies

IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY Mobile DNA Pub Date : 2022-01-01 DOI:10.4230/LIPIcs.DNA.28.1
T. Kennedy, Cadence Pearce, Chris Thachuk
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引用次数: 1

Abstract

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.
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快速和强大的链位移级联通过系统的设计策略
分子计算广泛应用的一个障碍是实现任意化学反应网络(crn)的困难,这些网络是稳健的,可以复制设计行为的动力学。DNA链位移(DSD)级联由于其模拟任意crn的潜力和调节其反应速率的已知原理,因此一直是一种受欢迎的技术。无泄漏级联的进展表明,当纳入系统域级冗余时,dsd可以对虚假的“泄漏”反应具有任意鲁棒性。鲁棒性的这些改进导致设计反应的动力学变慢。现有的工作已经证明了置换过程中序列失配的引入和消除对动力学和热力学的影响。我们提出了一种系统的、序列修改策略来优化无泄漏级联的动力学,而不会对其鲁棒性造成实际损失。一个深入的案例研究探讨了这种优化在应用于典型的无泄漏翻译器级联时的效果。能量势垒的热力学分析和动力学实验数据支持了DSD级联的快速和鲁棒性。
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来源期刊
Mobile DNA
Mobile DNA GENETICS & HEREDITY-
CiteScore
8.20
自引率
6.10%
发文量
26
审稿时长
11 weeks
期刊介绍: Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
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