The Monod, Wyman, Changeux model [ 3] is used for modeling an allosteric enzyme with two additional allosteric parameters: L (partition of active and inactive enzymes) and c (affinity of substrate to the inactive enzyme).
An application is presented basing on a model of an allosteric domain of mGluR4 receptor [3] – a challenging computational task, due to untrivial evolutionary relationships for homology model construction purposes, and shortage of experimental data for hypotheses validation.
Our model suggests an allosteric mechanism to UPR induction.
This model requires an allosteric response of the macromolecule (if KC = 0, then α = 1).
Interestingly, one noticeable feature of least some of the previous UPR models mentioned is that they involve a level of competition between components (Ron and Walter, 2007; Pincus et al., 2010); our present model suggests an allosteric mechanism at the heart of UPR induction.
We note that those types of observations gave rise to the models that evoke an allosteric influence of the state of the Qi site on the operation of the Qo site (27, 69, 70).
The plot illustrates that the Adair curve obtained from the parameters of the generalised MWC model presented here is similar to that obtained from experimental data, and that computing an Adair-Klotz function from the parameters of a MWC model does indeed provide a way of comparing an allosteric model to experimental measurements.
This framework has been used for an allosteric model of calmodulin [ 8], and could be useful in the analysis of a wide range of other proteins.
One case in which a conductance block may not be an accurate model is that of an allosteric drug block, in which a compound affects the ability of a channel to transition between open, closed, or inactivated states.
Together, the MD simulations and experimental data are consistent with an allosteric model of inhibition, wherein fatty acid binding induces a change in conformation that modifies the secondary structure of RRM1 and perturbs the position of amino acids required for RNA recognition.
