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Kinetic proofreading and the limits of thermodynamic uncertainty
Physical Review E ( IF 2.2 ) Pub Date : 2020-02-24 , DOI: 10.1103/physreve.101.022415
William D. Piñeros , Tsvi Tlusty

To mitigate errors induced by the cell's heterogeneous noisy environment, its main information channels and production networks utilize the kinetic proofreading (KPR) mechanism. Here, we examine two extensively studied KPR circuits, DNA replication by the T7 DNA polymerase and translation by the E. coli ribosome. Using experimental data, we analyze the performance of these two vital systems in light of the fundamental bounds set by the recently discovered thermodynamic uncertainty relation (TUR), which places an inherent trade-off between the precision of a desirable output and the amount of energy dissipation required. We show that the DNA polymerase operates close to the TUR lower bound, while the ribosome operates 5 times farther from this bound. This difference originates from the enhanced binding discrimination of the polymerase which allows it to operate effectively as a reduced reaction cycle prioritizing correct product formation. We show that approaching this limit also decouples the thermodynamic uncertainty factor from speed and error, thereby relaxing the accuracy-speed trade-off of the system. Altogether, our results show that operating near this reduced cycle limit not only minimizes thermodynamic uncertainty, but also results in global performance enhancement of KPR circuits.

中文翻译:

动力学校对和热力学不确定性的限制

为了减轻单元异类噪声环境引起的错误,其主要信息渠道和生产网络均采用了动态校对(KPR)机制。在这里,我们研究了两个经过广泛研究的KPR电路:通过T7 DNA聚合酶进行的DNA复制和通过大肠杆菌核糖体进行的翻译。使用实验数据,我们根据最近发现的热力学不确定性关系(TUR)设定的基本范围来分析这两个重要系统的性能,该关系在理想输出的精度和能量之间进行了固有的取舍。需要耗散。我们表明,DNA聚合酶接近TUR下限,而核糖体起作用5离此界限更远的时间。这种差异源于聚合酶结合分辨力的增强,使聚合酶能够有效地以缩短的反应周期有效地优先形成正确的产物。我们表明,接近此极限还会使热力学不确定性因素与速度和误差脱钩,从而放松了系统的精度-速度折衷。总而言之,我们的结果表明,在减小的循环极限附近运行不仅可以最大程度地降低热力学不确定性,而且可以提高KPR电路的整体性能。
更新日期:2020-02-24
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