生化钟多周期模型的鲁棒振荡
Robust oscillations in multi-cyclic models of biochemical clocks
摘要：
生物体经常利用化学物质浓度的周期性变化来精确地确定生物功能的时间。这些生化钟的基础是化学反应和运输过程，它们本质上是随机的。因此，了解在波动存在下的强大的生物化学振荡的物理基础已经成为一个重要的问题。在以前的论文[C。del Junco和S. Vaikuntanathan，Phys.Rev.E101，012410（2020）]，我们使用支持振荡的生物化学网络的单环马尔可夫状态模型的非平衡统计力学来探索这个问题。我们的发现是，他们可以利用非平衡驱动鲁棒地保持周期和振荡的一致性，在存在随机性的速率。在这里，我们将我们的工作扩展到马尔可夫状态模型由一个大周期装饰多个小周期。这些额外的周期是为了代表交替的路径，振荡器可能采取的，因为它波动的平均path.Combining映射到单周期网络的基础上首次通过时间分布与我们以前开发的理论，我们能够作出分析预测的周期和连贯性的振荡在这些网络。我们的预测的一个含义是，一个高的能量预算可以使不同的网络拓扑结构和安排的速率退化至于周期和振荡的相干性而言。分析和数值计算结果之间的良好协议证实了这一点。我们的研究结果表明，生化振荡器可以更强大的振荡器的路径波动时，他们有一个高的能量预算。
英文摘要：
Organisms often use cyclic changes in the concentrations of chemicals species to precisely time biological functions. Underlying these biochemical clocks are chemical reactions and transport processes, which are inherently stochastic. Understanding the physical basis for robust biochemical oscillations in the presence of fluctuations has thus emerged as an important problem. In a previous paper [C. del Junco and S. Vaikuntanathan, Phys. Rev. E 101, 012410 (2020)], we explored this question using the non-equilibrium statistical mechanics of single-ring Markov state models of biochemical networks that support oscillations. Our finding was that they can exploit non-equilibrium driving to robustly maintain the period and coherence of oscillations in the presence of randomness in the rates. Here, we extend our work to Markov state models consisting of a large cycle decorated with multiple small cycles. These additional cycles are intended to represent alternate pathways that the oscillator may take as it fluctuates about its average path. Combining a mapping to single-cycle networks based on first passage time distributions with our previously developed theory, we are able to make analytical predictions for the period and coherence of oscillations in these networks. One implication of our predictions is that a high energy budget can make different network topologies and arrangements of rates degenerate as far as the period and coherence of oscillations is concerned. Excellent agreement between analytical and numerical results confirms that this is the case. Our results suggest that biochemical oscillators can be more robust to fluctuations in the path of the oscillator when they have a high energy budget.
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