Homotrophic two-state model, HOTSM.

An agonist or substrate, S, can bind to two sterically separate sites in a receptor R. An unbound receptor in such a system can be in two conformations, an inactive form, R, and active form, R*. The displayed HOTSM is a thermodynamically complete reaction scheme for such a system. Bell-shaped dose-response relations, as for the IPP effect on γδ T cell proliferation, may be analyzed according to this HOTSM scheme. S = agonist. R and R* are receptor in inactive and active conformations respectively. L = the isomerization constant between unbound R* and R, L = R*/R. A_s = the equilibrium association constant for S at the orthosteric site of R. A_m = is equilibrium association constant for S at the allosteric site of R. a = efficacy constant for RS R*S when S is already bound to the orthosteric site. b = efficacy constant for SR SR* when S is already bound to the allosteric site. c = co-operativity coefficient for binding of S at either site to an already liganded R. d = co-operativity coefficient for efficacy induced by one ligand on binding when another ligand is already bound to R*s or an efficacy coefficient when two ligands are already bound