puckering free energies is a key requirement to perform proper simulations of those sugars which show an equilibrium between the two chair forms, but also for out-of-equilibrium sim- ulations of any sugar. Simulated pulling of polysaccharides, for example, has been proven to be an important tool for the interpretation of single molecule force-spectroscopy data $^{21,44,45}$, although the ring conformational transitions simulated using three different force fields (AMBER94 $^{46}$,AMBER-GLYCAM47 and CHARMM-Parm22/SU01 48 ) led to different in- terpretation of the same experimental data $^{21}$. Obviously, having control on the reliability of force fields in reproducing puckering properties would certainly improve all these kind of approaches. Even though the importance of reproducing correctly the population of ring conformers is quite broadly recognized, few attempts were made so far to investigate the problem in a systematic way and to understand the origin of the discrepancy between simulation results and experimental and theoretical findings (see for example Refs. 34,35,49). For this reason, we decided to study, employing a combined metadynamics – umbrella sampling approach $^{50}$, the puckering properties of simple α and β -d- aldopyranoses. We modeled the saccharides using he 45a4 carbohydrate parameter set 35 of the gromos force field, which shows incorrect population of conformers for many sugars, and we identified a new set of parameters that satisfactorily reproduces the free energies of the main ring conformers. This paper is organized as follows: in Sec. II the problems related to the determi- nation of puckering free energy landscape will be presented; in Sec. III the combined metadynamics–umbrella sampling will be discussed, as well as the use of Cremer–Pople puckering coordinates $^{51,52}$, their peculiarities as collective variables, and the simulation de- tails; in Sec. IV the puckering free energy profile obtained with the gromos 45a4 force field for β -d- glucose is discussed in detail and compared to recent similar calculations $^{43}$. In Sec V we present the puckering free energy profiles of the whole α and β series of d- aldohexoses modeled with the gromos 45a4 force field, showing that the puckering free energies are so poorly reproduced, that the inverted chair conformers of galactose, mannose and α -d- Glc become significantly populated. Subsequently, we propose a change to the 45a4 parameter set, showing how the free energies obtained with the use of the new parameter set compare favorably with available theoretical and experimental data. Eventually, some concluding remarks are presented in Sec. VI. 3