Searching for allosteric effects via QSAR. Part II Original Research Article

Allosteric interactions have in the past been established by means of X-ray crystallography or careful study of a single molecule at a variety of concentrations. Here we report a method for using QSAR to establish a change in reaction mechanism by establishing an inversion point. That is, as polarizability of a member of a congeneric set of compounds is increased (as measured by CMR), activity at first decreases until, at the inversion, activity turns around and increases. Out of 23 examples, 14 have inversion points of 10±1. This includes a wide variety of receptors such as thrombin, 5-HT, dopamine, and tyrosine kinase acting with a variety of ligands.