Interaction of noncompetitive inhibitors with the alpha3beta2 nicotinic acetylcholine receptor investigated by affinity chromatography and molecular docking

J Med Chem. 2007 Nov 29;50(24):6279-83. doi: 10.1021/jm070784s. Epub 2007 Oct 31.

Abstract

A molecular model of the alpha3beta2 nAChR lumen channel was constructed and hydrophobic clefts were observed near the receptor gate. Docking simulations indicated that ligand-nAChR complexes were formed by hydrophobic interactions with the cleft and hydrogen bond interactions. The equilibrium constants and association and dissociation constant rates associated with the binding interactions were determined using nonlinear chromatography on an immobilized alpha3beta2 nAChR column. The computational-chromatography approach can be used to predict and describe ligand-nAChR interactions.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • Chromatography, Liquid
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Models, Molecular*
  • Nicotinic Antagonists / chemistry*
  • Receptors, Nicotinic / biosynthesis
  • Receptors, Nicotinic / chemistry*
  • Structure-Activity Relationship

Substances

  • Ligands
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • nicotinic receptor alpha3beta2