Receptor grid was then generated with van der Waals radii scaling by 1, partial charge cutoff was set to 0.25, and halogens were enabled as donors. The active site was defined as the centroid of the co-crystallised ligand with innerbox of 10 Å 3 and outerbox of 24.076 Å 3 . OPLS_2005 forcefield was used and amide nitrogens of Gly116, Gly117, and Ala199 were defined as hydrogen donors. Ligand structures were prepared with LigPrep and ionised with Epik 78 (pH 7 ± 2) using OPLS4 force fieldbased on the known SAR, only the structures with ionised central tertiary amine were retained. Docking was performed using Glide XP with the following modifications of the default settings: intramolecular hydrogen bonds were rewarded, a constraint of at least one hydrogen bond formed as defined in the grid with an oxygen-based acceptor was introduced, and a maximum of 3 Å RMSD of the cycloheptyl ring in the docked poses (defined by C1CCCCCC1) vs. its position in the 6QAA cognate ligand. This led to poses that had carbamate alkyls oriented towards the acyl-binding pocket (case A). Additionally, another set of non-covalent docking conditions was used (case B): intramolecular hydrogen bonds were rewarded, a constraint of at least one hydrogen bond formed as defined in the grid with an oxygen-based acceptor was introduced, and a maximum of 1 Å RMSD of the indole ring in the docked poses (defined by RMSD subset atoms) vs. its position in the 6QAA cognate ligand. This approach led to poses that had carbamate alkyls oriented towards the cholinebinding pocket (case B). The output poses were visualised with Maestro.