Ligands affinity for regulatory sites of human acetylcholesterase and butyrylcholinesterase: A comparative bioinformatic analysis

Abstract

Cholinesterase inhibitors have been the subject of many studies aimed at developing an effective treatment for various cognitive disorders. Therefore, studying cholinesterases and elucidating the mechanism of their interaction with ligands provide a basis for targeted synthesis and selection of highly specific reversible inhibitors. We analyzed the affinity of the cholinesterase substrates and inhibitors to identify the differences in the ligands binding to the acetylcholinesterase and butyrylcholinesterase active sites by molecular docking. Ligands with a benzene ring had better affinity for the regulatory sites of acetylcholinesterase and butyrylcholinesterase. The lowest affinity for enzymes was found in choline, a hydrolysis product of natural acetylcholine, and in tetramethylammonium, a choline derivative. Differences in the binding of acetylcholine and choline molecules within the acyl pocket of the active site of cholinesterases were shown.