Grossfield. To emphasize the popularity of PMF calculation by the US method, based on data, the aforementioned publications related to the WHAM method are cited 700-800 times per year during the last five years. Compared to the number of total citations for the most popular MD softwares (AMBER, CHARMM, GROMACS, 38,45-47 NAMD ), being around 6000-11000 per year during the last five years, publications citing one of the PMF methods would correspond to approximately 7-11% of all MD papers (Figure ). Some recent examples of the ABFE calculation using the standard US approach include for example estimation of the free energy related to a cancer antigen binding to a protein, binding of DNA aptamers, small molecules binding to membranes, ligands binding to SARS-CoV-2, 56 and insulin dimer dissociation. With so many resources dedicated to computing binding free energies with US for problems with such high medical relevance, it is imperative that this approach yields accurate predictions.