For 0.5 M acetone in water, the calculated µ ′ sol values were -3.25 ± 0.03 and -6.09 ± 0.01 kcal mol -1 for acetone and water respectively. The average volume per acetone and water molecule was 3360 ± 0.9 and 31.5 ± 0.01 Å3 . For 0.1 M pyrimidine, the µ ′ sol values were -4.49 ± 0.02 and -6.09 ± 0.01 kcal mol -1 respectively. The average volume per pyrimidine and water molecule was 16312 ± 9 and 30.6 ± 0.01 Å3 . The average volume per ligand was calculated by recording the ratio of the number of ligands to box volume throughout a 5 ns NPT simulation at the appropriate concentrations.