Model preparation. Preparation and setup of the simulations were implemented using BAC , including parameterization of the compounds, solvation of the complexes, addition of counterions to electrostatically neutralize the systems and generation of configurations files for the simulations. The Amber package was used for the parameterisation of the compounds, the set-up of the systems, and the analyses of the results. The Amber ff14SB force field was used for the protein, and TIP3P for water molecules. The protonation states were assigned using the "reduce" module of AmberTools. Parameters of the ligands were produced using the general Amber force field 2 (GAFF2) with Gaussian 16 to optimise compound geometries and to determine electrostatic potentials at the Hartree-Fock level with 6-31G** basis functions.