Kinetic Proofreading and the Limits of Thermodynamic Uncertainty

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 $\sim 5$ 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.

arXiv commentMain text: 9 pages, 6 figures. 2 tables; no supplementary information

References in corpus (20)

• Thermodynamic uncertainty relation for biomolecular processes
• Dissipation bounds all steady-state current fluctuations
• Broken detailed balance and non-equilibrium dynamics in living systems
• Proof of the Finite-Time Thermodynamic Uncertainty Relation for Steady-State Currents
• Fluctuation theorem uncertainty relation
• Universal bound on the efficiency of molecular motors
• Theory of nonequilibrium free energy transduction by molecular machines
• Energetic costs, precision, and efficiency of a biological motor in cargo transport
• Stochastic thermodynamics: From principles to the cost of precision
• Universal Bound on the Fano Factor in Enzyme Kinetics
• Thermodynamics of Error Correction
• Physical insight into the thermodynamic uncertainty relation using Brownian motion in tilted periodic potentials
• The thermodynamics of computational copying in biochemical systems
• High fidelity of RecA-catalyzed recombination: a watchdog of genetic diversity
• General technique of calculating drift velocity and diffusion coefficient in arbitrary periodic systems
• Affinity- and topology-dependent bound on current fluctuations
• Protein-DNA computation by stochastic assembly cascade
• An energy-speed-accuracy relation in complex networks for biological discrimination
• Thermodynamics of accuracy in kinetic proofreading: Dissipation and efficiency trade-offs
• High-Fidelity DNA Sensing by Protein Binding Fluctuations

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