Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems
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DOI：
10.1098/rsif.2018.0107
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发表时间：
2018-12-01
影响因子：
3.9
通讯作者：
Winfree, Erik
中科院分区：
文献类型：
--
作者：
Berleant, Joseph;Berlind, Christopher;Winfree, Erik
作为工程材料，DNA非常适合生化电路和系统的构建，因为它很简单，可以使用Watson-Crick Base配对规则合理设计其交互作用，但设计空间非常丰富。在设计DNA系统时，这种简单性允许使用每个链（称为域）的功能切片，而无需考虑特定的核苷酸序列。但是，所使用的实际序列可能具有在域级抽象上预测的相互作用，并且需要新的严格分析技术来确定所选序列符合系统域级别的描述的程度。我们已经开发了一种计算方法来通过识别域级别和序列级别行为之间的差异来验证序列级系统。该方法采用了使用域级工具辣椒指定的DNA系统，并分析了从随机序列级模拟器多仪和序列级热力学分析工具Nupack中的数据，以估计系统的重要方面，例如反应速率常数和反应速率常数和反应速率常数和二级结构形成。这些技术以python包的方式实施，将使研究人员能够在序列分配后预测域级系统的动力学和热力学行为，并发现违反了预期的行为。
As an engineering material, DNA is well suited for the construction of biochemical circuits and systems, because it is simple enough that its interactions can be rationally designed using Watson-Crick base pairing rules, yet the design space is remarkably rich. When designing DNA systems, this simplicity permits using functional sections of each strand, called domains, without considering particular nucleotide sequences. However, the actual sequences used may have interactions not predicted at the domain-level abstraction, and new rigorous analysis techniques are needed to determine the extent to which the chosen sequences conform to the system's domain-level description. We have developed a computational method for verifying sequence-level systems by identifying discrepancies between the domain-level and sequence-level behaviour. This method takes a DNA system, as specified using the domain-level tool Peppercorn, and analyses data from the stochastic sequence-level simulator Multistrand and sequence-level thermodynamic analysis tool NUPACK to estimate important aspects of the system, such as reaction rate constants and secondary structure formation. These techniques, implemented as the Python package KinDA, will allow researchers to predict the kinetic and thermodynamic behaviour of domain-level systems after sequence assignment, as well as to detect violations of the intended behaviour.