CONFORMATIONAL ANALYSIS OF THE ACYL POCKET LOOP IN ACETYLCHOLINESTERASE COMPUTED BY MONTE CARLO METHODS WITH A GENERALIZED BORN MODEL OF

Acetylcholinesterase catalyzes the hydrolysis of the neurotransmitter, called acetylcholine. Based on X-ray crystallography, the acyl pocket loop (APL; residues 287 to 290) was observed in two conformations, the native conformation (2ACE) and an alternative conformation (2DFP), which the APL interacts with an irreversible inhibitor. The free energy of the 2DFP state was 4 kcal/mol higher than that of the 2ACE state. The native state has a more favorable solvation free energy, due primarily to Arg 289 interactions. The information should be useful in the development of antidotes against biological and chemical warfare agents that target AChE