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

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.