We implemented the free energy from adaptive reaction coordinate forces (FEARCF) method and applied it to the conformational investigation of carbohydrate
ring puckering. The method allows for significantly enhanced sampling of reaction coordinate space. The free energies associated with the ring pucker motion of β‐D‐ribose (a furanose) and β‐D‐glucose (a pyranose) were calculated. These can be used to interpret catalytic mechanisms of glycosylases.