Nakagawa Masaki, Togashi Yuichi
Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University Higashi-Hiroshima, Japan.
Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima UniversityHigashi-Hiroshima, Japan; Research Center for the Mathematics on Chromatin Live Dynamics, Hiroshima UniversityHigashi-Hiroshima, Japan.
Front Physiol. 2016 Mar 24;7:89. doi: 10.3389/fphys.2016.00089. eCollection 2016.
Cell activities primarily depend on chemical reactions, especially those mediated by enzymes, and this has led to these activities being modeled as catalytic reaction networks. Although deterministic ordinary differential equations of concentrations (rate equations) have been widely used for modeling purposes in the field of systems biology, it has been pointed out that these catalytic reaction networks may behave in a way that is qualitatively different from such deterministic representation when the number of molecules for certain chemical species in the system is small. Apart from this, representing these phenomena by simple binary (on/off) systems that omit the quantities would also not be feasible. As recent experiments have revealed the existence of rare chemical species in cells, the importance of being able to model potential small-number phenomena is being recognized. However, most preceding studies were based on numerical simulations, and theoretical frameworks to analyze these phenomena have not been sufficiently developed. Motivated by the small-number issue, this work aimed to develop an analytical framework for the chemical master equation describing the distributional behavior of catalytic reaction networks. For simplicity, we considered networks consisting of two-body catalytic reactions. We used the probability generating function method to obtain the steady-state solutions of the chemical master equation without specifying the parameters. We obtained the time evolution equations of the first- and second-order moments of concentrations, and the steady-state analytical solution of the chemical master equation under certain conditions. These results led to the rank conservation law, the connecting state to the winner-takes-all state, and analysis of 2-molecules M-species systems. A possible interpretation of the theoretical conclusion for actual biochemical pathways is also discussed.
细胞活动主要依赖于化学反应,尤其是那些由酶介导的反应,这使得这些活动被建模为催化反应网络。尽管浓度的确定性常微分方程(速率方程)在系统生物学领域已被广泛用于建模目的,但有人指出,当系统中某些化学物种的分子数量较少时,这些催化反应网络的行为方式可能与这种确定性表示在性质上有所不同。除此之外,用省略数量的简单二元(开/关)系统来表示这些现象也是不可行的。由于最近的实验揭示了细胞中存在稀有化学物种,能够对潜在的少数分子现象进行建模的重要性正在得到认可。然而,大多数先前的研究都是基于数值模拟,用于分析这些现象的理论框架尚未得到充分发展。受少数分子问题的推动,这项工作旨在为描述催化反应网络分布行为的化学主方程开发一个分析框架。为了简单起见,我们考虑了由双体催化反应组成的网络。我们使用概率生成函数方法在不指定参数的情况下获得化学主方程的稳态解。我们得到了浓度的一阶和二阶矩的时间演化方程,以及在某些条件下化学主方程的稳态解析解。这些结果引出了秩守恒定律、从连接状态到胜者全得状态的转变,以及对双分子M物种系统的分析。我们还讨论了该理论结论对实际生化途径的一种可能解释。