Overall, the present approach seems to have significant limitations -most notably that the computational expense is considerable, and the resulting estimated solubility is quite inaccurate. Perhaps both of these may be surmountable; GPU-based free energy calculations can be dramatically faster potentially making an 8000 CPUhour calculation be 80 GPU hours which would amount to overnight on 8 GPUs, and perhaps this could be optimized via changes to simulation time and number of intermediate states. And with better force fields, perhaps accuracy could be improved; the AMOEBA-based approach of Schnieders shows considerable promise . Alteratively, other approaches may be of interest. Solubility has been predicted by simulations using pseudocritical paths (i.e., paths were molecular crystals are transformed in tractable Einstein crystal-like states between the ending states of the transformation ) and a single experimental reference point ), and with the aid of a thermodynamic cycle formed by the molecular crystal, the molecule in vacuum, and the solvated molecule .