Kinetic Proofreading and the Limits of Thermodynamic Uncertainty
Kinetic Proofreading and the Limits of Thermodynamic Uncertainty
复制标题
动力学校对和热力学不确定性的极限
DOI：
10.1101/845164
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Tsvi Tlusty
中科院分区：
文献类型：
--
作者：
W. Piñeros;Tsvi Tlusty
为了减轻细胞异质性噪声环境引起的错误，其主要信息通道和生产网络利用动力学校对（KPR）机制。在这里，我们研究了两种被广泛研究的KPR回路，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，我们根据最近发现的热力学不确定性关系（TUR）设定的基本界限分析了这两个重要系统的性能，该关系在理想输出的精度和所需的能量耗散量之间进行了固有的权衡。我们发现DNA聚合酶在靠近TUR下限的地方工作，而核糖体在离这个下限远5倍的地方工作。这种差异源于聚合酶的增强结合辨别，这使得它能够有效地作为一个减少的反应周期优先考虑正确的产物形成。我们表明，接近这个极限也将热力学不确定性因素从速度和误差中解耦，从而放松了系统的精度-速度权衡。总之，我们的研究结果表明，在这个简化的循环极限附近工作不仅可以最大限度地减少热力学不确定性，而且还可以提高KPR电路的整体性能。
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.
T 细胞中的 IL7 受体信号传导：数学建模视角。
DOI：
10.1002/wsbm.1447
发表时间：
2019
期刊：
Wiley interdisciplinary reviews. Systems biology and medicine
影响因子：
--
作者：
Park,Jung-Hyun;Waickman,AdamT;Reynolds,Joseph;Castro,Mario;Molina-París,Carmen
通讯作者：
Molina-París,Carmen
影响因子：
4.5
作者：
Kramer, Emily B.;Farabaugh, Philip J.
通讯作者：
Farabaugh, Philip J.
超准确且容易出错的核糖体在 tRNA 选择过程中利用了不同的机制。
影响因子：
16
作者：
Zaher,HaniS;Green,Rachel
通讯作者：
Green,Rachel