Using msesMD, the Fucα(14)GlcNAc free energy surfaces for both Le a (Figure ) and sLe a (Figure ) are near identical with similar well depths for all major regions. However, differences of over 1 kcal mol -1 are seen in the reweighted Galβ(1-3)GlcNAc surfaces. Interestingly, unlike the unbiased MD simulations, the msesMD results estimate the F 4 and G 4 wells to be more stable in Le a rather than sLe a by an average of 0.5 and 1.2 kcal mol -1 respectively. We note that errors in msesMD free energy estimates, the errors calculated via bootstrap sampling are generally within ± 0.25 kcal mol -1 (Supplementary Figure ).