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 pharmacological tool, are explored. The analysis of the molecular electrostatic potential (MEP) as well as of the shape of the molecular surface is performed by self-organizing neural networks. A distorted sandwich conformation of W84 is suggested to be the active form. The importance of the MEP for binding of these compounds could be established.
Holzgrabe
U
U
Pharmazeutisches Institut, Universität Bonn, Germany.
Wagener
M
M
Gasteiger
J
J
D000443:Alcuronium / Q000494:pharmacology; D000494:Allosteric Regulation; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D054833:Isoindoles; D008958:Models, Molecular; D016571:Neural Networks, Computer; D010797:Phthalimides / Q000494:pharmacology; D011487:Protein Conformation; D011976:Receptors, Muscarinic / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D012984:Software; D013499:Surface Properties; D014403:Tubocurarine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D054833:Isoindoles; D010797:Phthalimides; D011976:Receptors, Muscarinic; C013017:hexamethylenebis(dimethyl-(3-phthalimidopropyl)ammonium bromide); D005703:Gallamine Triethiodide; D000443:Alcuronium; D014403:Tubocurarine