We then chose to calculate the solubility of ASA due to its pharmacological importance and due to its relative complexity in comparison to previous molecular solids whose absolute free energies have been computed via EMM previously . As for α-methanol, this calculation required a large number of intermediate alchemical states and considerable computational cost -approximately 8000 CPU hours for a single absolute free energy calculation for the molecular solid, even with the crystal structure as input. Perhaps the number of intermediate states could be further optimized, but clearly a large number of intermediate simulations was required and thus considerable computational cost. Despite all of this, we still could not reproduce the experimental aqueous solubility of acetylsalicylic acid (ASA); experimentally it is modestly soluble, whereas our work would suggest it is essentially completely insoluble in water, likely due to force field limitations.