For any given alchemical prediction ∆G F EP and associated experimental free energy ∆G EXP , ∆G of f set is defined as the difference between the two; it also constitutes the training label for the given perturbation. This method relies on the assumption that given a training set of sufficient size, an empirical model trained on this set will be able to estimate accurately ∆G of f set values for a new set of alchemical predictions, thereby compensating for systematic errors in the underlying alchemical methodology.