Allosteric interactions and QSAR: on the role of ligand hydrophobicity.

A study of a very large database of QSAR (9100) has uncovered a few unusual examples where as one increases the hydrophobicity of the members of a set of congeners, activity decreases until at a certain point, activity begins to increase. Obviously a change in mechanism is involved. The only way we have found to rationalize this unusual event is by a change in the structure of the receptor. We have found this to occur with hemoglobin, a substance first used to define allosteric reactions.