Tunable kinetic proofreading in a model with molecular frustration

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 non-trivial specificity amplification. We show that this mechanism can be seen as a more general form of a kinetic proofreading (KP) mechanism, with an interesting new property, namely the ability to tune the specificity amplification by changing the reactants concentrations. This contrasts with the classical KP 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 KP mechanisms, with even richer properties. These models can find applications in different areas such as evolutionary biology, immunology, and biochemistry.