Design principles for robust oscillatory behavior.
Design principles for robust oscillatory behavior.
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DOI：
10.1007/s11693-015-9178-6
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发表时间：
2015-09-01
期刊：
影响因子：
--
通讯作者：
Coronado, Alberto M
中科院分区：
文献类型：
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作者：
Castillo-Hair, Sebastian M;Villota, Elizabeth R;Coronado, Alberto M
振荡反应在生物体的调节网络中普遍存在，这一事实导致了广泛的研究和复制所涉及的电路的努力。然而，到目前为止，自然振荡器的鲁棒性的设计原则并不完全清楚。在这里，我们研究了一个三组分酶网络模型，以确定鲁棒振荡的拓扑要求。首先，通过模拟每一种可能的拓扑结构并改变它们的参数值，我们证明了鲁棒振荡器可以通过增加负反馈回路和正自调节回路的数量来获得，同时保持正负相互作用的适当平衡。然后，我们确定网络图案，其存在于更复杂的拓扑结构是获得振荡响应的必要条件。最后，我们确定了一系列简单的架构模式，逐步呈现更强大的振荡器。总之，这些发现可以帮助设计更可靠的合成生物分子网络，也可能对理解其他振荡系统产生影响。
Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems.