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信号转导网络的模拟进化。

Simulated evolution of signal transduction networks.

机构信息

Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany.

出版信息

PLoS One. 2012;7(12):e50905. doi: 10.1371/journal.pone.0050905. Epub 2012 Dec 12.

Abstract

Signal transduction is the process of routing information inside cells when receiving stimuli from their environment that modulate the behavior and function. In such biological processes, the receptors, after receiving the corresponding signals, activate a number of biomolecules which eventually transduce the signal to the nucleus. The main objective of our work is to develop a theoretical approach which will help to better understand the behavior of signal transduction networks due to changes in kinetic parameters and network topology. By using an evolutionary algorithm, we designed a mathematical model which performs basic signaling tasks similar to the signaling process of living cells. We use a simple dynamical model of signaling networks of interacting proteins and their complexes. We study the evolution of signaling networks described by mass-action kinetics. The fitness of the networks is determined by the number of signals detected out of a series of signals with varying strength. The mutations include changes in the reaction rate and network topology. We found that stronger interactions and addition of new nodes lead to improved evolved responses. The strength of the signal does not play any role in determining the response type. This model will help to understand the dynamic behavior of the proteins involved in signaling pathways. It will also help to understand the robustness of the kinetics of the output response upon changes in the rate of reactions and the topology of the network.

摘要

信号转导是细胞在接收到来自环境的刺激时,将信息路由到细胞内部的过程,从而调节细胞的行为和功能。在这种生物过程中,受体在接收到相应的信号后,会激活许多生物分子,这些分子最终将信号转导到细胞核。我们工作的主要目标是开发一种理论方法,该方法将有助于更好地理解由于动力学参数和网络拓扑结构的变化而导致的信号转导网络的行为。我们使用进化算法设计了一个数学模型,该模型执行类似于活细胞信号转导过程的基本信号任务。我们使用相互作用蛋白及其复合物的信号网络的简单动力模型。我们研究了由质量作用动力学描述的信号网络的进化。网络的适应性由一系列强度不同的信号中检测到的信号数量决定。突变包括反应速率和网络拓扑结构的变化。我们发现,更强的相互作用和新节点的添加会导致改进的进化响应。信号的强度在确定响应类型方面没有任何作用。该模型将有助于理解参与信号通路的蛋白质的动态行为。它还有助于理解在反应速率和网络拓扑结构变化时,输出响应的动力学的稳健性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/546a/3521023/0fe580d0a003/pone.0050905.g001.jpg

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