The SEEKR2 and QMrebind+SEEKR2 methods reproduce the rank ordering for receptor-ligand unbinding rates for the seven host-guest complexes (Figure ). However, improved accuracies in estimating k off rates for the host-guest complexes are achieved with the QMrebind+SEEKR2 approach. SEEKR2 simulations with the generic force field tend to slightly overestimate the k off values for all host-guest complexes, while QMrebind helps to correct this overestimation, resulting in k off rates that are in closer agreement with experimental measurements (Figure ). Additionally, comparable convergences of k off rates for QMrebind+SEEKR2 simulations with reparameterized force fields and SEEKR2 simulations employing generic force fields are observed (Supplementary Figure ). For all the seven host-guest complexes, QMre-bind+SEEKR2 consistently outperformed SEEKR2 in estimating k off rates. Such improvements can likely be attributed to more accurate force field parameters for the ligand within the vicinity of the host molecule, as computed by the QMrebind software.