Programming Substrate-Independent Kinetic Barriers With Thermodynamic Binding Networks
Programming Substrate-Independent Kinetic Barriers With Thermodynamic Binding Networks
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DOI：
10.1109/tcbb.2019.2959310
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发表时间：
2021-01-01
影响因子：
4.5
通讯作者：
Soloveichik, David
中科院分区：
文献类型：
--
作者：
Breik, Keenan;Chalk, Cameron;Soloveichik, David
表现出复杂行为的工程分子系统需要动力学屏障的设计。例如，在没有催化剂的情况下，有效的催化途径必须具有较大的势垒。虽然编程这样的能量屏障似乎需要特定的分子底物的知识，我们开发了一种新的底物无关的方法。我们扩展了最近开发的称为热力学结合网络的模型，展示了仅由键形成的热力学驱动力和形成单独配合物的构型熵产生的可编程动力学障碍。我们的动力学模型做了相对较弱的假设，这意味着我们模型预测的能量势垒将存在于各种各样的系统和条件中。我们通过显示其定义的几个变化导致等效能量势垒来证明我们的模型是鲁棒的。我们应用这个模型来设计具有任意大能垒的非催化反应的催化体系。我们的研究结果可以利用DNA链位移产生强大的放大器，这是一种工程合成反应途径的流行技术，并提出了在各种分子系统中防止不良动力学行为的设计策略。
Engineering molecular systems that exhibit complex behavior requires the design of kinetic barriers. For example, an effective catalytic pathway must have a large barrier when the catalyst is absent. While programming such energy barriers seems to require knowledge of the specific molecular substrate, we develop a novel substrate-independent approach. We extend the recently-developed model known as thermodynamic binding networks, demonstrating programmable kinetic barriers that arise solely from the thermodynamic driving forces of bond formation and the configurational entropy of forming separate complexes. Our kinetic model makes relatively weak assumptions, which implies that energy barriers predicted by our model would exist in a wide variety of systems and conditions. We demonstrate that our model is robust by showing that several variations in its definition result in equivalent energy barriers. We apply this model to design catalytic systems with an arbitrarily large energy barrier to uncatalyzed reactions. Our results could yield robust amplifiers using DNA strand displacement, a popular technology for engineering synthetic reaction pathways, and suggest design strategies for preventing undesired kinetic behavior in a variety of molecular systems.