论文标题

与输出抑制作用的反基础积分(REN)控制的结构稳定性特性

Structural Stability Properties of Antithetic Integral (Rein) Control with Output Inhibition

论文作者

Briat, Corentin, Khammash, Mustafa

论文摘要

完美的适应是一种精心研究的生化稳态行为,位于生化调节的核心。尽管体内平衡和完美适应的概念并不是什么新鲜事物,但它们的基本机制和相关的生化调节基序尚未完全了解。控制理论的见解揭示了完美适应与整体控制之间的联系,这是一种普遍的工程控制策略。特别是,最近引入的反基础积分控制器(AIC)已被证明可以成功确保与其连接到网络的完美适应性。 AIC所依赖的两个分子的互补结构允许一种多功能的方法来控制生化网络,这一特性引起了与数学上有关的重要文献,从而在数学上阐明其特性,推广其结构并开发实验方法以实施其实施。对立的积分控制器(AIRC)是AIC的扩展,其中两个控制器分子都用于对照,它具有许多诺言,因为它据说克服了AIC的某些局限性。我们在这里专注于具有输出抑制的AIRC结构,该结构将两个AIC结合在单个结构中。我们证明了RHIS控制器在轻度假设下确保对受控网络的结构稳定性和结构完美适应性,这意味着该属性独立于网络和控制器的参数。结果对于单分子质量表演网络以及包括合作社和Michaelis-Menten网络在内的更通用网络的类别非常通用和有效。我们还提供了一种系统且易于访问的计算方式,用于验证给定网络是否满足结构属性所持的条件。

Perfect adaptation is a well-studied biochemical homeostatic behavior lying at the core of biochemical regulation. While the concepts of homeostasis and perfect adaptation are not new, their underlying mechanisms and associated biochemical regulation motifs are not yet fully understood. Insights from control theory unraveled the connections between perfect adaptation and integral control, a prevalent engineering control strategy. In particular, the recently introduced Antithetic Integral Controller (AIC) has been shown to successfully ensure perfect adaptation properties to the network it is connected to. The complementary structure of the two molecules the AIC relies upon allows for a versatile way to control biochemical networks, a property which gave rise to an important body of literature pertaining to mathematically elucidating its properties, generalizing its structure, and developing experimental methods for its implementation. The Antithetic Integral Rein Controller (AIRC), an extension of the AIC in which both controller molecules are used for control, holds many promises as it supposedly overcomes certain limitations of the AIC. We focus here on an AIRC structure with output inhibition that combines two AICs in a single structure. We demonstrate that rhis controller ensure structural stability and structural perfect adaptation properties for the controlled network under mild assumptions, meaning that this property is independent of the parameters of the network and the controller. The results are very general and valid for the class of unimolecular mass-action networks as well as more general networks, including cooperative and Michaelis-Menten networks. We also provide a systematic and accessible computational way for verifying whether a given network satisfies the conditions under which the structural property would hold.

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