Biocircuits Institute, University of California, San Diego, La Jolla, CA, USA.
Biophys J. 2010 Nov 17;99(10):3172-81. doi: 10.1016/j.bpj.2010.09.057.
A major challenge for systems biology is to deduce the molecular interactions that underlie correlations observed between concentrations of different intracellular molecules. Although direct explanations such as coupled transcription or direct protein-protein interactions are often considered, potential indirect sources of coupling have received much less attention. Here we show how correlations can arise generically from a posttranslational coupling mechanism involving the processing of multiple protein species by a common enzyme. By observing a connection between a stochastic model and a multiclass queue, we obtain a closed form expression for the steady-state distribution of the numbers of molecules of each protein species. Upon deriving explicit analytic expressions for moments and correlations associated with this distribution, we discover a striking phenomenon that we call correlation resonance: for small dilution rate, correlations peak near the balance-point where the total rate of influx of proteins into the system is equal to the maximum processing capacity of the enzyme. Given the limited number of many important catalytic molecules, our results may lead to new insights into the origin of correlated behavior on a global scale.
系统生物学的一个主要挑战是推断潜在的分子相互作用,这些相互作用是导致不同细胞内分子浓度之间观察到相关性的基础。尽管通常会考虑直接的解释,如转录偶联或直接的蛋白质-蛋白质相互作用,但潜在的间接耦合来源受到的关注要少得多。在这里,我们展示了如何通过涉及共同酶对多种蛋白质种类进行加工的翻译后耦合机制,普遍产生相关性。通过观察随机模型和多类队列之间的联系,我们获得了每种蛋白质种类的分子数量的稳态分布的封闭形式表达式。在推导出与该分布相关的矩和相关性的显式解析表达式之后,我们发现了一个惊人的现象,我们称之为相关性共振:对于小的稀释率,相关性在平衡点附近达到峰值,此时蛋白质流入系统的总速率等于酶的最大处理能力。鉴于许多重要催化分子的数量有限,我们的结果可能会为全球范围内相关行为的起源提供新的见解。