The "up" rotamer of F280 is observed in the inactive sub-ensemble of PTP1B "reference" more than it is in the active (Figure ). Compound 2 lacks a arylsulfonamide-thiazole moiety to wrap around F280, and consequently F280 adopts multiple rotameric states during the simulations (Figure and Figure green). The most populated "down" rotamer of F280 observed during simulations of 2r is similar to the major rotamer observed in the active sub-ensemble of PTP1B "reference" simulations (Figure green χ 1 angle ca. -180 deg. and Figure , orange). Such differences in behaviour in F280 dynamics are not apparent in crystal structures of 1 and 2 (PDB IDs 1T4J and 1T48) where F280 adopts a "down" rotamer exclusively (Figure , dashed lines).