Appropriately choosing which 6 atoms to involve in Boresch-style 70 orientational restraints can be a complex issue, here we use the procedure as implemented in MDRestraintsGenerator (10.5281/zenodo.4570555). Briefly, we pick out the least mobile ligand atoms from our final 20 ns equilibration simulation (see System Equilibration above) as potential anchor points for our orientational restraint. We then analyse the trajectory to select all available alpha carbon protein anchor atoms within an 8 Å cut-off of the ligand anchor atoms, generating a list of potential orientational restraints (where the nearest bonded ligand heavy atoms and protein backbone atoms are selected as the remaining atoms involved in the orientational restraint).