Mathematical Medicine and Biology: A Journal of the IMA
We show how equilibrium binding curves of receptor homodimers can be expressed as rational polynomial functions of the equilibrium binding curves of the constituent monomers, without approximation and without assuming independence of receptor monomers. Using a distinguished spanning tree construction for reduced graph powers, the method properly accounts for thermodynamic constraints and allosteric interactions between receptor monomers (i.e. conformational coupling). The method is completely general; it begins with an arbitrary undirected graph representing the topology of a monomer state-transition diagram and ends with an algebraic expression for the equilibrium binding curve of a receptor oligomer composed of two or more identical and indistinguishable monomers. Several specific examples are analysed, including guanine nucleotide-binding protein-coupled receptor dimers and tetramers composed of multiple ‘ternary complex’ monomers.
Conradi Smith, Gregory D., Allostery in Oligomeric Receptor Models (2020). Mathematical Medicine and Biology: A Journal of the IMA, 37(3), 313-333.
bioRxiv preprint doi: https://doi.org/10.1101/330571; this version posted March 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.