OPLS/AA parameters were assigned using the LigParGen web server . CM1A charges were used and three rounds of optimization were performed. Rifampicin could not be parameterized in the neutral state and was therefore omitted in the MD simulations in water with OPLS/AA. For lorlatinib, the dihedral-angle term for the cyano group N#CC-X had to be removed because it is poorly defined as the cyano group is linear.