Thermodynamic limits in far-from-equilibrium molecular templating networks

Benjamin Qureshi; Jenny M Poulton; Thomas E Ouldridge

doi:10.1016/j.newton.2025.100302

Thermodynamic limits in far-from-equilibrium molecular templating networks

Newton. 2026 Jan 5;2(1):None. doi: 10.1016/j.newton.2025.100302.

Authors

Benjamin Qureshi^{1

2}, Jenny M Poulton³, Thomas E Ouldridge^{1

2}

Affiliations

¹ Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
² Centre for Engineering Biology, Imperial College London, London SW7 2AZ, UK.
³ Department of Physics and Astronomy, University of Sheffield, Sheffield S3 7RH, UK.

Abstract

Cells maintain a highly specific, far-from-equilibrium population of RNA and protein molecules. They do so via complex reaction networks in which templates catalyze the assembly of desired products. We show that information transmission from templates to products in such networks is bounded by functions of the maximal difference in free-energy changes between assembly pathways. Surprisingly, putative systems operating at the bounds do not have a high net flux around the network, as is typical in far-from-equilibrium systems and observed in biology. Instead, the upper bound on accuracy for a given network structure is achieved in "pseudo-equilibrium." Here, each product is produced and degraded by time-reversed trajectories along a single (product-specific) pathway with negligible entropy production; product yields are determined by the free-energy changes along those pathways. The limit imposed by these free-energy changes induces a thermodynamic constraint on accuracy, even if a single templating process is arbitrarily kinetically selective.

Keywords: molecular networks; molecular templating; non-equilibrium biophysics; stochastic thermodynamics; thermodynamics of information.