In all cases, we did not calculate the marginal standard error for the last 10 % of the data, to avoid noisy estimates producing very late truncation. Each method was applied to every member of the synthetic ensembles after truncating the synthetic data after 8 ns, which is fairly typical of an absolute binding free energy calculation. In addition to the "Standard" datasets (8 ns truncation and generated as described above), we tested all methods on a "Short" dataset where the truncation point was 0.2 ns, a "Subsampled" dataset where 99 of every 100 datapoints were discarded, a "Noisy" dataset where the autocovariance terms were scaled up by