A third biasing approach, accelerated molecular dynamics (aMD), was also employed for comparison. We report the free energy surface for sLe a in explicitly modelled water, obtained using dual boost aMD. In this approach, a boost potential is applied based on the total and dihedral potential energies of the system. To compare with the eight msesMD replicas, we combine the results of eight independent 494 ns aMD simulations to obtain the final free energy surfaces (Figure ). The aMD simulations provide good coverage of the Fucα(14)GlcNAc and Galβ(1-3)GlcNAc glycosidic linkages, identifying all the main wells, F 1-4 and G 1-5 , in addition to an high energy F 5 well not seen in either unbiased MD or msesMD simulations. However, as demonstrated by the  F and  G time series (Figure ), the F 4 and G 4 wells appear to be infrequently sampled.