In this work, we have benchmarked two hyperparameters of our workflow: the initial and able to further optimize these protocols for efficiency or accuracy. In cases where significant reorganization of the protein occurs upon ligand annihilation, it may be necessary to increase the maximum simulation lengths or by integrating more advanced enhanced sampling methods such as Hamiltonian exchange molecular dynamics into the workflow. The development of an on-thefly optimal λ-schedule would further assist in increasing the efficiency of these calculations; however, this specific problem is beyond the scope of this work and will be addressed in the future.