Computational cost savings for both the protein-ligand complex and solvated ligand steps were calculated by taking 10,000 independent samples of a particular batch size of each mutation and summing up the total number of production nanoseconds of a batch of a given mutation for a given alchemical step. For Protocols A, B, and C, the complement of this number divided by 120 was taken, representing the total number of nanoseconds simulated by Song et al. for a given mutation multiplied by two to account for their use of 1 fs time step. For Protocol C12, the complement of the sum simulation time divided by 60 was used. Mean and standard errors of savings were calculated from these distributions. Summary statistics of these savings are shown in Table .