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存在错误增强药物时的误差传播模型。

A model of error propagation in the presence of an error-enhancing drug.

作者信息

Johansson J, Blomberg C

机构信息

Department of Theoretical Physics, Royal Institute of Technology, Stockholm, Sweden.

出版信息

J Theor Biol. 1995 Mar 7;173(1):1-13. doi: 10.1006/jtbi.1995.0037.

Abstract

A mathematical model is considered that describes error propagation in protein synthesis, with emphasis on the role of an error-enhancing drug such as streptomycin. The subject of error propagation has been investigated in a number of works since an original proposal by Orgel in 1963. From experiments, it is known that streptomycin given to a bacterium culture in small concentration increases the error level, but at a certain concentration threshold the bacteria die. This two-fold behavior has, in some papers, lead to the proposal that another effect of the drugs besides that of error propagation leads to the death of the bacteria. In the present work, we use a model related to kinetic models of selection in protein synthesis which include the combined effect of ribosome and synthetase action. The model shows very clear threshold effects: for small values of the parameter that represents the drug action, a stable situation is found that has an increased error level but still attains a rather high accuracy. At a certain threshold, this is no longer maintained. The main emphasis here is on the time evolution of relevant parameters, and it is also shown how this can be quite drastic: the accuracy may decrease rather smoothly to a critical point, where it is drastically lost and where the bacteria may die out very suddenly.

摘要

我们考虑了一个描述蛋白质合成中错误传播的数学模型,重点关注诸如链霉素等错误增强药物的作用。自1963年奥格尔最初提出以来,错误传播这一主题已在许多研究中得到探讨。从实验中可知,向细菌培养物中添加低浓度的链霉素会提高错误水平,但在某个浓度阈值时细菌会死亡。在一些论文中,这种双重行为导致有人提出,药物除了错误传播作用之外的另一种效应会导致细菌死亡。在本研究中,我们使用了一个与蛋白质合成中选择动力学模型相关的模型,该模型包括核糖体和合成酶作用的综合效应。该模型显示出非常明显的阈值效应:对于代表药物作用的参数的较小值,会发现一种稳定状态,其错误水平增加,但仍能达到相当高的准确性。在某个阈值时,这种状态不再维持。这里主要强调相关参数的时间演化,并且还展示了这种演化可能有多剧烈:准确性可能相当平稳地下降到一个临界点,在该点准确性会急剧丧失,细菌可能会非常突然地灭绝。

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