Modeling of substrates sorption into acetylcholinesterase and butyrylcholinesterase active sites using molecular docking method

Cholinesterases (ChE) acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are capable for hydrolyzing esters. Our previous structure-activity analysis of ChE substrates showed that extended conformation of substrate choline moiety is productive for hydrolysis by AChE and its semi-folded conformation is productive for hydrolysis by BChE. The formation of activated complex between ChE and substrate molecules is possible only when the substrate molecule is in the productive conformation [1]. The purpose of the present work was to model sorption stage of ChE hydrolysis and to determine the substrate orientation of a substrate in the binding site of AChE and BChE using molecular docking and computer simulation methods.