COMPARISON OF STRUCTURALLY DIFFERENT ALLOSTERIC MODULATORS OF MUSCARINIC RECEPTORS BY SELF-ORGANIZING NEURAL NETWORKS

Similarities in the molecular structure and surface properties of the allosteric modulators of muscarinic receptors, alcuronium, gallamine, tubocurarine, and the hexamethonium compound W84, a well-known pharmac ological tool, are explored. The analysis of the molecular electrostat ic potential (MEP) as well as of the shape of the molecular surface is pei-formed by self-organizing neural networks. A distorted sandwich c onformation of W84 is suggested to be the active form. The importance of the MEP for binding of these compounds could be established. (C) 19 96 by Elsevier Science Inc.