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Classical versus Stochastic Kinetics Modeling of Biochemical Reaction Systems

机译:生化反应系统的经典动力学与随机动力学建模

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摘要

We study fundamental relationships between classical and stochastic chemical kinetics for general biochemical systems with elementary reactions. Analytical and numerical investigations show that intrinsic fluctuations may qualitatively and quantitatively affect both transient and stationary system behavior. Thus, we provide a theoretical understanding of the role that intrinsic fluctuations may play in inducing biochemical function. The mean concentration dynamics are governed by differential equations that are similar to the ones of classical chemical kinetics, expressed in terms of the stoichiometry matrix and time-dependent fluxes. However, each flux is decomposed into a macroscopic term, which accounts for the effect of mean reactant concentrations on the rate of product synthesis, and a mesoscopic term, which accounts for the effect of statistical correlations among interacting reactions. We demonstrate that the ability of a model to account for phenomena induced by intrinsic fluctuations may be seriously compromised if we do not include the mesoscopic fluxes. Unfortunately, computation of fluxes and mean concentration dynamics requires intensive Monte Carlo simulation. To circumvent the computational expense, we employ a moment closure scheme, which leads to differential equations that can be solved by standard numerical techniques to obtain more accurate approximations of fluxes and mean concentration dynamics than the ones obtained with the classical approach.
机译:我们研究具有基本反应的一般生化系统的经典和随机化学动力学之间的基本关系。分析和数值研究表明,内在波动可能定性和定量地影响瞬态和平稳系统的行为。因此,我们提供了内在波动可能在诱导生化功能中发挥作用的理论理解。平均浓度动力学受与经典化学动力学相似的微分方程控制,以化学计量矩阵和随时间变化的通量表示。但是,每个通量都被分解为一个宏观术语和一个介观术语,该宏观术语解释了平均反应物浓度对产物合成速率的影响,而介观术语则解释了相互作用之间的统计相关性。我们证明,如果不包括介观通量,则模​​型解释由内在波动引起的现象的能力可能会受到严重损害。不幸的是,通量和平均浓度动力学的计算需要大量的蒙特卡洛模拟。为了避免计算费用,我们采用了矩闭环方案,该方案可以通过标准数值技术求解微分方程,从而获得比传统方法更精确的通量和平均浓度动力学近似值。

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