Scalable Rule-Based Modelling of Allosteric Proteins and Biochemical Networks
Figure 3
Classic and general models of allostery and protein structure are described by our modelling framework.
(A) A concerted model of a tetrameric allosteric protein has one allosteric component and 4 identical interaction sites to represent each subunit. The dashed lines indicate that each ligand-binding site is a modifier for the R↔T allosteric transition and all 4 interactions are identically parameterized by ΦLB. (B) In a sequential model of the protein, a top-level hierarchical component comprises 4 identical allosteric components that individually change conformation and bind ligand. These components are allosterically coupled (dashed lines) such that each subunit is equivalent and a modifier for all neighbouring subunits – the “tetrahedral” model. The strength of the coupling is given by the regulatory factor ΓS and the effect of each modifier on the kinetics of coupled components is parametrized by ΦLB and ΦS. (C) Altered lateral interactions between subunits gives the “square” model. (D) A tertiary two-state model has one allosteric hierarchical component containing 4 identical allosteric components, each with a ligand-binding site. The upper quaternary component is allosterically coupled to each tertiary component with strength Γ and the tertiary components are coupled to their binding site. The effect of the quaternary conformation on the kinetics of the tertiary transition is given by ΦQ, and the reciprocal interaction is parameterized by ΦT. (E) The ligand for all four models. (F) Rules for the concerted model in panel A. (G) Rules for the models in panels B, C and D.