Influence of ligand binding on the conformation of Torpedo californica acetylcholinesterase

With the aim of identifying structural changes in acetylcholinesterase, ind uced by ligand binding, we use a completely automatic procedure to analyse the differences between the backbone conformation of the free enzyme and th ose in eight complexes of Torpedo californica acetylcholinesterase, with va rious quaternary ammonium ligands, and with the protein inhibitor fasciculi n. In order to discriminate between structural changes due to ligand bindin g and those arising from model imprecision, we also examine protein-ligand and protein-water contacts. Except for the peptide Aip in the complex with huperzine A, the backbones of other complexes with quaternary ammonium liga nds display negligible changes relative to the free enzyme. Another excepti on is the complex with the bisquaternary ammonium ligand decamethonium, whe re several loops display above average deformations, but only two, those sp anning residues 334-348 and residues 277-304, seem to move! as a result of ligand binding. Movement of the omega loop (residues 61-95) is detected onl y in the complex with the protein fasciculin.