peformed ABFE calculations for 105 ligand-protein complexes using AMBER20 and demonstrated their capability to run such calculations with cloud computing resources . Chen et al. presented their ABFE predictions for 199 ligand-protein complexes using Schrödinger's FEP+ package . It should be noted that the reliability of FEP+ is questionable as its proprietary nature prevents reproducibility studies to be performed. Further, it employs the REST2 approach that is known to degrade the quality of predicted free energies . Unlike these two studies that employed equilibrium (EQ) simulations to obtain ABFEs, Khalak et al. used non-equilibrium (NEQ) simulations to obtain ABFE predictions for a set of 128 ligand-protein complexes .