to use two correction terms ∆G V and ∆G R , which reflect the change in the free energy when restraints are removed for the unbound and bound states, respectively. To check if the differences between individual repeats of the US simulations can be mitigated with such corrections, we calculated the correction terms for trypsin-benzamidine as in Doudou's paper and for HdeA dimer, as an example system with clearly different pathways. For both systems, the computed correction terms were almost identical for all repeats (Table ),