. . . λ N overlap between the intermediate states is computationally demanding. A 900-atom OPLS α-methanol system required 40 states to calculate ∆A id→I E M , and 600 states for ∆A I E M →solid . We chose these intermediate states in advance, and these ultimately led to free energy errors smaller than 0.1 k B T; the estimated TI and MBAR values differed by no more than 0.3 k B T. Our results for ASA using an optimal number of states can be seen in Table . The MBAR chemical potential of ASA at 298.15 K equals to -220.67(3) k B T. The computational cost of calculating A ASA was high; Each state required a separate simulation (of a 1344-atom ASA system), with 718 states in total. Simulations typi-cally required 11 hours on a single CPU, so the calculation of a single absolute free energy of a molecular solid required approximately 7898 CPU-hours.