β -cyclodextrin (host) is a cyclic oligosaccharide characterized by a toroidal shape formed by seven glucopyranose units linked by . This macrocyclic molecule possesses a hydrophobic cavity in its central core, which can effectively encapsulate one of the ligand (guest) molecules of suitable size and shape, thus stabilizing their molecular structures and altering their physicochemical properties. These properties make βcyclodextrin an ideal model system for studying host-guest interactions using novel approaches. The shape, size, and functional groups of the guest molecules affect their binding to the host cavity. Additionally, these ligands have different binding affinities for the host, allowing it to rank-order them according to their unbinding (k off ) rates. The host with seven different ligands, including alcohols (1-butanol, 1-naphtylethanol, 2naphtylethanol, 1-propanol, and tert-butanol) and esters (aspirin and methyl-butyrate) served as model receptor-ligand complexes for evaluating the effectiveness of the reparameterized force field parameters of the receptor-ligand complexes in the SEEKR2 algorithm (Figure ). Receptor-ligand unbinding rates are calculated using the QMrebind+SEEKR2 algorithm and compared against the previously performed SEEKR2 simulations, without QMrebind reparameterization, and experimentally determined unbinding k off rates.