The CF-SMD simulation may play an important role in estimating the fast dissociation time, which cannot be experimentally detected. Unlike large molecules, small molecules have weak binding affinities. This makes the detection of kinetics challenging. For instance, the small molecules-DMSO, DSS, and BUT-bound to FKBP dissociate so fast that experimental methods have difficulty in detecting the kinetics, whereas CF-SMD simulation can quantify such rapid dissociation times in a reasonable computational time. We believe that CF-SMD simulation is advantageous for the characterization of weak binders, contributing to fragment-based drug design .