While none of the aforementioned averaging procedures is ideal, we nevertheless applied them to estimate free energies from our simulations. The difference between the approaches is 4.7 kcal/mol, with averaging over the results from the repeats with equal weights providing the highest estimate (18.2 kcal/mol), while the lowest estimate (13.4 kcal/mol) was obtained by averaging with the Boltzmann weights. The exponential averaging yields a value of 14.3 kcal/mol (Figure ). The results of different averaging approaches for the other systems can be found in Table , and the corresponding Figures .