Title: Kinetic Proofreading and the Limits of Thermodynamic Uncertainty Show Chinese title

Title: 动能校对与热力学不确定性的极限

Abstract: 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 $\sim5$ 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. Show Chinese abstract

Abstract: 为减轻由细胞异质噪声环境引起的误差，其主要信息通道和生产网络利用了动能校对（KPR）机制。 在这里，我们研究了两种广泛研究的KPR电路，即T7 DNA聚合酶的DNA复制和大肠杆菌核糖体的翻译。 利用实验数据，我们在最近发现的热力学不确定性关系（TUR）所设定的基本界限下，分析了这两个关键系统的性能，该关系将期望输出的精度与所需能量耗散量之间存在固有的权衡。 我们表明，DNA聚合酶接近TUR下限，而核糖体则远离这一界限$\sim5$倍。 这种差异源于聚合酶增强的结合鉴别能力，使其能够有效地作为优先生成正确产物的简化反应循环运行。 我们表明，接近这个极限还可以使热力学不确定性因子与速度和误差解耦，从而缓解系统的准确性-速度权衡。 总的来说，我们的结果表明，在这个简化循环极限附近运行不仅最小化了热力学不确定性，还提高了KPR电路的整体性能。