Comparing the relative free energy profiles for Le x and sLe x generated by msesMD (Figure ), sialylation appears to impact the stability of the F 4 and G 4 conformers, with an estimated 0.9 and 0.7 kcal mol -1 average decrease in stability respectively going from Le x to sLe x (Figure and 8b). Interestingly, as discussed above, the msesMD simulations for Le a and sLe a also predict a decrease in stability for the F 4 and G 4 wells upon sialylation. This may indicate that sialylation stiffens the Fuc-GlcNAc and Gal-GlcNAc linkages, preventing the large ~ 140-200° flips in the ψ angle associated with these two wells.