Tunable kinetic proofreading in a model with molecular frustration

TL;DR

This paper introduces a tunable kinetic proofreading mechanism based on molecular frustration, allowing specificity amplification to be adjusted via reactant concentrations, unlike traditional fixed-rate models.

Contribution

It demonstrates that molecular frustration can create a flexible kinetic proofreading system with adjustable specificity, expanding understanding of feedback mechanisms in complex biochemical systems.

Findings

Molecular frustration can induce nontrivial feedback loops.

Specificity amplification can be tuned by reactant concentrations.

The model generalizes classical kinetic proofreading mechanisms.

Abstract

In complex systems, feedback loops can build intricate emergent phenomena, so that a description of the whole system cannot be easily derived from the properties of the individual parts. Here we propose that inter-molecular frustration mechanisms can provide non trivial feedback loops which can develop nontrivial specificity amplification. We show that this mechanism can be seen as a more general form of a kinetic proofreading mechanism, with an interesting new property, namely the ability to tune the specificity amplification by changing the reactants concentrations. This contrasts with the classical kinetic proofreading mechanism in which specificity is a function of only the reaction rate constants involved in a chemical pathway. These results are also interesting because they show that a wide class of frustration models exists that share the same underlining kinetic proofreading mechanisms, with even richer properties. These models can find applications in different areas such as evolutionary biology, immunology and biochemistry.