Here, we attempt to improve the efficiency of ABFE calculations by developing and evaluating automated protocols in each of the areas mentioned: the spacing of intermediate states, the allocation of sampling time, and the detection of equilibration. Where possible, we use ensemble-based metrics to increase robustness. We have sought to minimise user time, in addition to computational time, by implementing our protocols in an easy-to-use open-source python package, A3FE, which is itself based on BioSimSpace and SOMD. 2 Theory