Binding sites of acetylcholine in the aromatic gorge leading to the active site of acetylcholinesterase

Theoretical calculations performed on the interactions of acetylcholine with the aromatic gorge of acetylcholinesterase indicate the existence of a number of local minima for the substrate. These minima are clustered in four regions of increasing interactions from top to bottom of the gorge, culminating in the region of the active site. The results allow the delineation of the role of the different aminoacids lining the walls, emphasizing, in particular, that of Trp 279 and Trp 84 while smaller interactions involve tyrosines 70, 121, 130, 334 and Phe 330. The influence of D72 is stressed, as well as the orientating role of A 201 and the strong driving influence of E199.