No starting model was able to sustain the initial geometry (Figure ). Only free BChE with protonated Glu197 (from now on Glh) and DEP-hBChE with Glh441 showed mostly converging behavior (Figure ). In both cases, the stable conformation was substantially different from the x-ray reference. A recurring feature was Asn322 losing its h-bond to the backbone oxygen of Met437 and switching to interact with the catalytic Glu325. If Glu441 were to harbor a proton, it would be bound to the upper oxygen of the carboxylate group as can be clearly seen from the electron density (Figure ). However, in dynamics Glh441 always flipped (Figure ). Glh197 in corresponding models switched to h-bond Glu441 directly.