Kinetic vs. energetic discrimination in biological copying

TL;DR

This paper compares kinetic and energetic discrimination mechanisms in biological copying, showing their exclusive nature in single-step reactions and analyzing their effects on error rates, velocity, and dissipation, with implications for DNA polymerases.

Contribution

It demonstrates that kinetic and energetic discrimination are mutually exclusive in single-step copying and explores their distinct effects on error reduction, velocity, and energy dissipation.

Findings

Kinetic and energetic discrimination are strictly alternative in single-step reactions.

Kinetic discrimination leads to diverging velocity and dissipation near the error limit.

Energetic discrimination achieves minimal error with vanishing dissipation and velocity.

Abstract

We study stochastic copying schemes in which discrimination between a right and a wrong match is achieved via different kinetic barriers or different binding energies of the two matches. We demonstrate that, in single-step reactions, the two discrimination mechanisms are strictly alternative and can not be mixed to further reduce the error fraction. Close to the lowest error limit, kinetic discrimination results in a diverging copying velocity and dissipation per copied bit. On the opposite, energetic discrimination reaches its lowest error limit in an adiabatic regime where dissipation and velocity vanish. By analyzing experimentally measured kinetic rates of two DNA polymerases, T7 and Pol{\gamma}, we argue that one of them operates in the kinetic and the other in the energetic regime. Finally, we show how the two mechanisms can be combined in copying schemes implementing error correction through a proofreading pathway