For the free ligands, both the autocorrelation and blocking analyses yield SEM estimates of <0.1 kcal/mol (Table ), for both the individual and combined duplicate runs, A and B. In addition, the blocking curves show appropriate plateaus (Panels b and d in Figures and), and the duplicate runs provide mean energies that deviate from their combined mean by 0.09 kcal/mol on average. (Mean potential energies and blocking graphs for the combined A and B runs are provided in the SI.) Thus, the free ligand energies are well-converged by all measures, even for the individual 20µs simulations.