3D MODEL OF THE ACETYLCHOLINESTERASE CATALYTIC CAVITY PROBED BY STEREOSPECIFIC ORGANOPHOSPHOROUS INHIBITORS

Automated docking was performed for stereospecific and quasi-irreversi ble organophosphorous acetylcholinesterase (AChE) inhibitors. Twelve c hiral inhibitor structures, corresponding to six enantiomeric pairs, e ach with a phosphorus atom as a stereocentre, were docked to the cryst al structure of mouse AChE. This study gives evidence that in inhibito rs with different aromatic and cationic leaving groups these groups ar e oriented towards the entry of the active site, as recently suggested by Hosea et al [1] for inhibitors with a thiocholine leaving group. T he results of the docking were used to establish a three dimensional m odel of the volume sterically available to the inhibitors within the A ChE active site.