CONFORMATIONAL FLEXIBILITY AND RECEPTOR INTERACTION

This theoretical analysis shows that the experimentally observed stand ard Gibbs free energy of binding of a ligand by a receptor can be desc ribed by two terms. One term describes the free energy of binding of t he drug to the receptor when both are in their lowest energy conformat ion. The second term gives the difference between the average and the lowest conformational energy of the two species involved. It also foll ows that all drug molecules having an energy higher than the minimum e nergy, must have a higher affinity than molecules occurring in the min imum energy conformation, independent of the energy level of the recep tor bound conformation. (C) 1998 Elsevier Science Ltd. All rights rese rved.