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结合序列信息对蛋白质合成速率进行公式化表述。

Formulation of the protein synthesis rate with sequence information.

作者信息

Xia Wenjun, Lei Jinzhi

机构信息

Faculty of Science, Jiangsu University, Zhenjiang, Jiangsu 212013, China email:

Zhou Pei-Yuan Center for Applied Mathematics, MOE Key Laboratory of Bioinformatics, Tsinghua University, Beijing, 100084, China email:

出版信息

Math Biosci Eng. 2018 Apr 1;15(2):507-522. doi: 10.3934/mbe.2018023.

Abstract

Translation is a central biological process by which proteins are synthesized from genetic information contained within mRNAs. Here, we investigate the kinetics of translation at the molecular level by a stochastic simulation model. The model explicitly includes RNA sequences, ribosome dynamics, the tRNA pool and biochemical reactions involved in the translation elongation. The results show that the translation efficiency is mainly limited by the available ribosome number, translation initiation and the translation elongation time. The elongation time is a log-normal distribution, with the mean and variance determined by the codon saturation and the process of aa-tRNA selection at each codon binding site. Moreover, our simulations show that the translation accuracy exponentially decreases with the sequence length. These results suggest that aa-tRNA competition is crucial for both translation elongation, translation efficiency and the accuracy, which in turn determined the effective protein production rate of correct proteins. Our results improve the dynamical equation of protein production with a delay differential equation that is dependent on sequence information through both the effective production rate and the distribution of elongation time.

摘要

翻译是一种核心生物学过程,通过该过程可从mRNA中包含的遗传信息合成蛋白质。在此,我们通过一个随机模拟模型在分子水平上研究翻译动力学。该模型明确包含RNA序列、核糖体动力学、tRNA库以及翻译延伸过程中涉及的生化反应。结果表明,翻译效率主要受可用核糖体数量、翻译起始和翻译延伸时间的限制。延伸时间呈对数正态分布,其均值和方差由密码子饱和度以及每个密码子结合位点处的氨酰-tRNA选择过程决定。此外,我们的模拟表明,翻译准确性随序列长度呈指数下降。这些结果表明,氨酰-tRNA竞争对于翻译延伸、翻译效率和准确性都至关重要,而这反过来又决定了正确蛋白质的有效蛋白质产生速率。我们的结果通过一个延迟微分方程改进了蛋白质产生的动力学方程,该方程通过有效产生速率和延伸时间分布依赖于序列信息。

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