In general, we note the somewhat flatter topology features of the reweighted aMD free energy surfaces relative to msesMD and unbiased MD, which are particularly evident around the F 1-3 and G 1-3 regions (Figure ). This may be a reflection of the magnitude of the resultant aMD boost energy, which has a mean and range of 4.9 and 24.2 kcal mol -1 respectively; this compares to an applied swarm energy for msesMD of mean 4.1 kcal mol -1 and range 18.4 kcal mol -1 (Figure ).