Although the CF-SMD simulation provides the dissociation time of a ligand in equilibrium, the calculation of the association rate (𝑘 +< ) remains unresolved. The calculation is considerably difficult, and only a few studies have been successful. It has been performed only for weak binders to proteins and protein-protein association by brutally long-time MD simulations or by indirect calculation from the binding free energy and 𝑘 +,, value . One exception is the recent work by Wolf et al., who proposed the novel idea that dissipated-corrected targeted molecular dynamics (TMD) simulation is combined with one-dimensional Langevin dynamics. They provided reasonable 𝑘 +< , 𝑘 +,, , and binding free energy . Although such a method has been devised, much work is necessary to develop an effective method to predict the kinetics of association and dissociation events using non-equilibrium MD simulations.