Breik Keenan, Chalk Cameron, Doty David, Haley David, Soloveichik David
IEEE/ACM Trans Comput Biol Bioinform. 2021 Jan-Feb;18(1):283-295. doi: 10.1109/TCBB.2019.2959310. Epub 2021 Feb 3.
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.
设计具有复杂行为的分子系统需要设计动力学屏障。例如，有效的催化途径在没有催化剂时必须有一个大的屏障。虽然编程这样的能量屏障似乎需要特定分子底物的知识，但我们开发了一种新颖的与底物无关的方法。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复合物的构象熵产生的可编程动力学屏障。我们的动力学模型做出的假设相对较弱，这意味着我们模型预测的能量屏障将存在于各种各样的系统和条件中。我们通过表明其定义中的几种变化导致等效的能量屏障来证明我们的模型是稳健的。我们应用这个模型来设计对未催化反应具有任意大能量屏障的催化系统。我们的结果可以使用DNA链置换产生稳健的放大器，DNA链置换是一种用于工程合成反应途径的流行技术，并为防止各种分子系统中不期望的动力学行为提供设计策略。
