In this study, we heavily relied on x-ray structures as references for the extended active site geometry. Some calculations directly used positional restraints. The bias that originates with the limitations in resolution and inaccuracies of refinement is propagated to MD. Furthermore, hBChE entry 1P0I that is commonly used for molecular replacement -even for presumably unliganded forms -features a chemically modified catalytic serine. This model itself used phases from 2ACE, a tcAChE structure also harboring a modified Ser residue. hAChE models are also traced down to tcAChE model 1FSS. Therefore, there may be less similarities between free and ligand-bound forms and between hAChE and hBChE that are currently observable in PDB. Further advancements in purification and Cryo-EM may present new insights into the structures of cholinesterases that will help rectify the results obtained herein.