error bars of 0.4 kJ/mol). This fact could in principle be exploited to fix the C3–C2–C1–O1 interaction so that it reproduces the gap between the $^{1}$C$_{4}$ free energies of α and β idose. In practice, however, we were unable to proceed along this line, because we did not manage to obtain satisfactorily puckering properties for idose and all other sugars at the same time. This could be related either to the fact that, admittedly, we did not perform a complete exploration of the parameter space due to the high demand of computational resources of this task or, to the fact that also non-bonded interactions should be re-parametrized, given the complex interplay typical of effective force fields. Eventually, some additional corrections were made by adding the same kind of torsional interaction on the dihedral C4–C3–C2–O2, which is related to the position of the substituent at the chiral carbon C2. In summary, the phase and amplitude of the C3–C2–C1–O1, C4–C3–C2–O2, C1–C2–C3– O3, C5–C4–C3–O3 and C1–O5–C5–C6 torsional interaction were tuned by trial and errors in order to obtain $^{1}$C$_{4}$ free energy curves in better agreement with experimental and theoretical data. The set of torsional interactions and their parameters for the proposed modification to the 45a4 parameter set a re reported in Tab. IV. It is worth mentioning that the strength of the C1–C2–C3–O3 and C5–C4–C3–O3 torsional interactions had to be set to a much higher value (2.4 kJ/mol) than that of the other ones involving three ring atoms and one hydroxyl oxygen. Given the similar chemical nature of the quadruplets of atoms involved (beside that of the anomeric oxygen), such asymmetry appears to be peculiar. This might originate from other interaction terms already present in the 45a4 set, whose influence on the puckering free energy is not yet understood, and that might deserve a separate investigation. The new parametrization of the gromos force field for sugars was performed with the aim not to change properties other than puckering, and dihedral interactions directly involved in the rotameric distribution of the hydroxymethyl group were thus not changed. This choice alone, however, is no guarantee that this quantity is not affected We checked explicitly that these modifications did not affect the rotameric distribution of the hydroxymethyl group, calculating the free energy profile of the C4–C5–C6–O6 torsional angle for the 45a4 and new sets of parameters. The results obtained with the two parameter sets did not differ more than 2% between each other. The free energy surfaces have been calculated employing the same metadynamics/umbrella sampling approach employed for the calculation of the puckering free energy, but using a Gaussian width of 0.1 rad. We summarized the results obtained using our modified set of parameters in Figs. 7,8,9 21