As we explain in more detail in the Results section, successful absolute free energy calculations for molecular solids require a pathway involving a large number of alchemical intermediate states. The calculation of the absolute free energies of α-methanol at 150 K and acetylsalicylic acid required 600 states. Since GROMACS reads each λ until its fourth decimal place and the states need to be spaced more closely together as as the harmonic restraints are turned off (See Supporting Information), we decided to split each free energy calculation in sets of 100 states.