Computing phenomenologic Adair-Klotz constants from microscopic MWC parameters

Background: Modellers using the MWC allosteric framework have often found it difficult to validate their models. Indeed many experiments are not conducted with the notion of alternative conformations in mind and therefore do not (or cannot) measure relevant microscopic constant and parameters. Instead, experimentalists widely use the Adair-Klotz approach in order to describe their experimental data. Results: We propose a way of computing apparent Adair-Klotz constants from microscopic association constants and allosteric parameters of a generalised concerted model with two different states (R and T), with an arbitrary number of non-equivalent ligand binding sites. We apply this framework to compute Adair-Klotz constants from existing models of calmodulin and hemoglobin, two extreme cases of the general framework. Conclusion: The validation of computational models requires methods to relate model parameters to experimentally observable quantities. We provide such a method for comparing generalised MWC allosteric models to experimentally determined Adair-Klotz constants.