Interplay of energy, dissipation, and error in kinetic proofreading: Control via concentration and binding energy

TL;DR

This paper investigates how energy, dissipation, and error are interconnected in kinetic proofreading, revealing how control via concentration and binding energy influences the trade-offs and efficiency of biological error correction mechanisms.

Contribution

It introduces a nonequilibrium steady state theory combined with thermodynamics to analyze the energetic and dynamic features of proofreading networks, highlighting optimal operating regions and trade-offs.

Findings

Dissipation-error trade-off domain correlates with error rate basin.

Energy control via chemical fuel influences proofreading efficiency.

Optimal energy content approaches a nominal value in trade-off regimes.

Abstract

Kinetic proofreading mechanisms explain the extraordinary accuracy observed in central biological events in terms of the enhanced specificity of substrate selection networks under a nonequilibrium environment. The nonequilibrium steady state theory incorporated with a chemical thermodynamic framework is implemented to execute a systematic investigation of dynamic and thermodynamic features of the proofreading network under continuous fuel consumption. We have identified that the dissipation-error trade-off domain of the network has a one-to-one correspondence with the deeper portion of the basin-like error rate profile depicted here. Further, quantifying the energy cost through concentration control of the chemical fuel aids in unveiling the association of the energy and chemical work with the optimal operating region of the biological error-correcting mechanism. It is shown that the proper energy content of the system, the semigrand Gibbs free energy, approaches a nominal value in the trade-off regime, whereas it gets considerably minimized in the domain with a lack of trade-off. We have also introduced a performance measuring entity corresponding to different energetic discrimination magnitudes as a product of average dissipation and coefficient of variation for the whole range of chemical fuel. Besides invoking a different perspective to the experimental and theoretical assessment of biological processes like DNA replication or protein synthesis, our findings can be advantageous in designing more efficient synthetic biological architectures.