The effect of electrostatic interactions on the absorption of the positively charged reversible inhibitor tetramethylammonium, its neutral structural analogue neopentane C(CH(3))(4), and the natural substrate acethylcholine to the active sites of acetylcholinesterase and butyrylcholinesterase has been studied by molecular modeling methods. It has been shown that the dominant absorption of positively charged ligands is due to the anchoring of the cationic group of the ligand in the anionic subsite of both enzymes through the interaction of the pi-cation with the benzene ring of tryptophan. The correlation between the free energy of complex formation and the catalytic activity of charged tetramethylammonium has been revealed for both enzymes. It has been shown that the effective binding of the acetylcholine molecule requires the additional activation of the enzyme.