The CovDock protocol was used for covalent docking of the carbamate ligands and the fluorophore-labelled products of the click reaction. We again used the prepared 6QAA crystal structure, His438 residue was manually modified to charged HIP438 to ensure the proper postreaction structure, and Ser198 was negatively ionised. Ser198 was selected as the reactive residue, the box was defined as the centroid of the co-crystallised ligand in 6QAA with the size defined by the ligand. Reaction type was customised using a custom chemistry file (see Supporting Information) to correctly produce a negatively charged tetrahedral intermediate, since the default nucleophilic addition to a double bond led to a neutral one. No constraints were imposed and the thorough pose prediction docking mode was used. The results were visualised in Maestro and the obtained docking poses with cycloheptyl ring outside its welldefined position above Trp82 (vide supra) or with the ex-carbonyl anionic oxygen located outside the oxyanion hole were removed. The remaining poses were ranked by score and favourable interactions with the peripheral site residues (Tyr332, Asp70). For the case B poses, the prereaction poses from non-covalent docking were manually modified (bond formed between the carbonyl carbon and Oγ-Ser198, and its length set to optimal, His438 protonated on Nε, double bond of the carbonyl changed to single, and carbonyl oxygen negatively charged) to produce the corresponding postreaction states that were later used for MD.