Comparison of structurally different allosteric modulators of muscarinic receptors by self-organizing neural networks

J Mol Graph. 1996 Aug;14(4):185-93, 217-21. doi: 10.1016/s0263-7855(96)00060-4.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcuronium / pharmacology
  • Allosteric Regulation
  • Cholinesterase Inhibitors / pharmacology
  • Gallamine Triethiodide / pharmacology
  • Isoindoles
  • Models, Molecular
  • Neural Networks, Computer
  • Phthalimides / pharmacology
  • Protein Conformation*
  • Receptors, Muscarinic / chemistry*
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology
  • Software
  • Surface Properties
  • Tubocurarine / pharmacology

Substances

  • Cholinesterase Inhibitors
  • Isoindoles
  • Phthalimides
  • Receptors, Muscarinic
  • hexamethylenebis(dimethyl-(3-phthalimidopropyl)ammonium bromide)
  • Gallamine Triethiodide
  • Alcuronium
  • Tubocurarine