Efficiency parameters in artificial allosteric systems

Abstract

It is shown that the until now largely overlooked change of the conformational energy ΔG_C is the dominating factor for most synthetic allosteric complexes. Essential is the energy ΔG_C required for the formation of a suitable geometry for ligand binding in the absence of an effector molecule E; ΔG_C is usually dominated by an increase of strain and/or by high energy solvents in a cavity. The role of the effector molecule E in such systems is to generate a suitable conformation for binding the ligand A and thus to compensate the unfavourable conformational energy ΔG_C. Positive cooperativity increases with ΔG_C, and decreases with the ΔG_0(A) value which reflects the binding energy of A in a strain-free host. As illustrated with a few examples ΔG_0(A) cannot be measured directly but can eventually be estimated independently. Many artificial allosteric systems described in the literature, such as those based on ethylene glycol chains or bipyridyl units, lack significant strain differences, and are therefore less efficient. Negative cooperativity is determined only by the difference ΔΔG_A,E between the binding energies at the two sites; it can be enhanced or lowered by concomitant changes in ΔG_C.