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Classic and contemporary approaches to modeling biochemical reactions.

机译:用于模拟生化反应的经典方法和当代方法。

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摘要

Recent interest in modeling biochemical networks raises questions about the relationship between often complex mathematical models and familiar arithmetic concepts from classical enzymology, and also about connections between modeling and experimental data. This review addresses both topics by familiarizing readers with key concepts (and terminology) in the construction, validation, and application of deterministic biochemical models, with particular emphasis on a simple enzyme-catalyzed reaction. Networks of coupled ordinary differential equations (ODEs) are the natural language for describing enzyme kinetics in a mass action approximation. We illustrate this point by showing how the familiar Briggs-Haldane formulation of Michaelis-Menten kinetics derives from the outer (or quasi-steady-state) solution of a dynamical system of ODEs describing a simple reaction under special conditions. We discuss how parameters in the Michaelis-Menten approximation and in the underlying ODE network can be estimated from experimental data, with a special emphasis on the origins of uncertainty. Finally, we extrapolate from a simple reaction to complex models of multiprotein biochemical networks. The concepts described in this review, hitherto of interest primarily to practitioners, are likely to become important for a much broader community of cellular and molecular biologists attempting to understand the promise and challenges of "systems biology" as applied to biochemical mechanisms.
机译:最近对生化网络建模的兴趣提出了以下问题:通常的复杂数学模型与经典酶学中熟悉的算术概念之间的关系,以及建模与实验数据之间的联系。这篇综述通过使读者熟悉确定性生化模型的构建,验证和应用中的关键概念(和术语),特别是简单的酶催化反应,从而解决了这两个主题。耦合常微分方程(ODE)的网络是描述质量作用近似中的酶动力学的自然语言。我们通过展示熟悉的Michaelis-Menten动力学的Briggs-Haldane公式如何从描述特定条件下简单反应的ODE动力学系统的外部(或准稳态)解决方案中得出这一点来说明这一点。我们讨论如何从实验数据中估计Michaelis-Menten近似值和基础ODE网络中的参数,并特别强调不确定性的起源。最后,我们从简单的反应推断为多蛋白生化网络的复杂模型。迄今为止,本综述中所描述的概念主要是从业者感兴趣的,对于试图了解应用于生化机制的“系统生物学”的希望和挑战的细胞和分子生物学家来说,它可能变得更为重要。

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