Computational Design of Nucleic Acid Feedback Control Circuits
Computational Design of Nucleic Acid Feedback Control Circuits
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DOI：
10.1021/sb400169s
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发表时间：
2014-08-01
影响因子：
4.7
通讯作者：
Phillips, Andrew
中科院分区：
文献类型：
--
作者：
Yordanov, Boyan;Kim, Jongmin;Phillips, Andrew
设计控制分子尺度过程的合成电路是合成生物学的一个重要目标，在未来的体外和体内生物技术中具有潜在的应用。在本文中，我们提出了一个计算方法设计的反馈控制电路构造的核酸。我们的方法依赖于现有的方法来表达信号处理和控制电路作为生物分子反应。我们首先扩展的方法，使电路可以表示使用两类反应：催化和湮灭。然后，我们提出了这些反应在三个不同类别的核酸电路，这依赖于DNA链置换，DNA酶和RNA酶的机制，分别实现。我们使用这些实现来设计比例积分控制器，能够根据给定的参考信号调节系统的输出，并讨论不同方法之间的权衡。作为原理的证明，我们将我们的方法作为DNA链置换软件工具的扩展来实现，从而允许在一个共同的建模框架内设计和分析广泛的核酸电路。
The design of synthetic circuits for controlling molecular-scale processes is an important goal of synthetic biology, with potential applications in future in vitro and in vivo biotechnology. In this paper, we present a computational approach for designing feedback control circuits constructed from nucleic acids. Our approach relies on an existing methodology for expressing signal processing and control circuits as biomolecular reactions. We first extend the methodology so that circuits can be expressed using just two classes of reactions: catalysis and annihilation. We then propose implementations of these reactions in three distinct classes of nucleic acid circuits, which rely on DNA strand displacement, DNA enzyme and RNA enzyme mechanisms, respectively. We use these implementations to design a Proportional Integral controller, capable of regulating the output of a system according to a given reference signal, and discuss the trade-offs between the different approaches. As a proof of principle, we implement our methodology as an extension to a DNA strand displacement software tool, thus allowing a broad range of nucleic acid circuits to be designed and analyzed within a common modeling framework.