Department of Applied Science and Technology, Politecnico di Torino corso Duca degli Abruzzi 24, Turin, IT-10129, Italy.
Italian Institute for Genomic Medicine, via Nizza 52, I-10126, Torino, Italy.
Sci Rep. 2018 Jul 10;8(1):10387. doi: 10.1038/s41598-018-28647-9.
Many biological processes are known to be based on molecular sequestration. This kind of dynamics involves two types of molecular species, namely targets and sequestrants, that bind to form a complex. In the simple framework of mass-action law, key features of these systems appear to be threshold-like profiles of the amounts of free molecules as a function of the parameters determining their possible maximum abundance. However, biochemical processes are probabilistic and take place in stochastically fluctuating environments. How these different sources of noise affect the final outcome of the network is not completely characterised yet. In this paper we specifically investigate the effects induced by a source of extrinsic noise onto a minimal stochastic model of molecular sequestration. We analytically show how bimodal distributions of the targets can appear and characterise them as a result of noise filtering mediated by the threshold response. We then address the correlations between target species induced by the sequestrant and discuss how extrinsic noise can turn the negative correlation caused by competition into a positive one. Finally, we consider the more complex scenario of competitive inhibition for enzymatic kinetics and discuss the relevance of our findings with respect to applications.
许多生物过程都基于分子隔离。这种动力学涉及两种类型的分子物种,即靶标和隔离剂,它们结合形成复合物。在质量作用定律的简单框架中,这些系统的关键特征似乎是作为决定其最大丰度的参数的函数的自由分子数量的阈值状分布。然而,生化过程是概率性的,并且发生在随机波动的环境中。这些不同的噪声源如何影响网络的最终结果还不完全清楚。在本文中,我们专门研究了一种外源性噪声源对分子隔离的最小随机模型的诱导效应。我们分析地展示了靶标如何出现双峰分布,并将其特征化为由阈值响应介导的噪声滤波的结果。然后,我们研究了隔离剂引起的目标物种之间的相关性,并讨论了外源性噪声如何将竞争引起的负相关转化为正相关。最后,我们考虑了酶动力学中竞争性抑制的更复杂情况,并讨论了我们的发现与应用的相关性。