Distinct alchemical methods differing in approach, energy model, and/or sampling technique were used to submit ranked predictions for the cyclodextrins and phenothiazine challenge. The methods used were ATM, DDM, and potential of mean force (PMF). The accuracy of ranked methods as measured by RMSE and MAE ranged from 1.86 to 27.26 kcal/mol, and 1.60 to 26.38 kcal/mol, respectively. The ranked methods were ordered based on these accuracy metrics as shown in Figure , with ATM/FFENGINE/TIP3P/HREM emerging as the top performing method.