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Robustness of a Reconstituted Escherichia coli Protein Translation System Analyzed by Computational Modeling
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-07-13 00:00:00 , DOI: 10.1021/acssynbio.8b00228
Tomoaki Matsuura 1 , Kazufumi Hosoda 2 , Yoshihiro Shimizu 3
Affiliation  

Robustness against environmental changes is one of the major features of biological systems, but its origin is not well understood. We recently constructed a large-scale computational model of an Escherichia coli-based reconstituted in vitro translation system that enumerates all protein synthesis processes in detail. Our model synthesizes a formyl-Met-Gly-Gly tripeptide (MGG peptide) from 27 initial molecular components through 968 biochemical reactions. Among the 968 kinetic parameters, 483 are nonzero parameters, and the simulator was used to determine how perturbations of 483 individual reactions affect the complex reaction network. We found that even when the kinetic parameter was changed from 100- to 0.01-fold, 94% of the changes hardly affected the two indicators of reaction dynamics in MGG peptide synthesis, which represent the yield of the MGG peptide and the initial lag-time of the peptide synthesis. Moreover, none of the indicators increased proportionally to these changes: e.g., a 100-fold increase in the kinetic parameter increased the yield by only 2.2-fold at most, indicating the insensitivity of the reaction network to perturbation. Robustness and insensitivity are likely to be a common feature of large-scale biological reaction networks.

中文翻译:

通过计算模型分析重构的大肠杆菌蛋白质翻译系统的鲁棒性

抵御环境变化的鲁棒性是生物系统的主要特征之一,但其起源尚不清楚。我们最近构建了基于大肠杆菌体外重构的大规模计算模型详细列举所有蛋白质合成过程的翻译系统。我们的模型通过968个生化反应从27个初始分子成分合成了甲酰基-Met-Gly-Gly三肽(MGG肽)。在968个动力学参数中,有483个非零参数,并且使用模拟器确定了483个单个反应的扰动如何影响复杂的反应网络。我们发现,即使动力学参数从100倍变为0.01倍,也有94%的变化几乎不影响MGG肽合成中反应动力学的两个指标,这两个指标代表MGG肽的产量和初始滞后时间肽合成。而且,没有任何指标随这些变化成比例地增加:例如,动力学参数增加100倍,最多只能将产量提高2.2倍,表明反应网络对扰动不敏感。鲁棒性和不敏感性可能是大规模生物反应网络的共同特征。
更新日期:2018-07-13
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