Searching for allosteric effects via QSARs

A study of our database of 7,000 QSARs involving chemical-biological intera ction uncovered 11 examples where the QSARs all contain inverted parabolas based on molecular refractivity. That is, biological activity first decreas es with increase in MR and then increases. Two of the examples are for enzy mes: cyclooxygenase and trypsin. The others are for various receptors. The results seem to be best rationalized by the larger compounds inducing a cha nge in a receptor unit that allows for a new mode of interaction. (C) 2001 Elsevier Science Ltd. All rights reserved.