checked separately for each of them. For these reasons we decided to compute in a systematic way the puckering free energy landscape for the whole series of α and β -d- pyranoses. From the point of view of the force field, the stereoisomers of glucose differ only slightly, namely (a) the order of the two central atoms involved in an improper dihedral interaction at a chiral centre has to be inverted, in order to move a residue form the equatorial to the axial conformation; (b) α anomers are distinguished from β anomers by different torsional interactions on the O5–C1–O1–H1 dihedral, and (c) those sugars having O4 and C6 located on the same side of the ring plane (galactose, talose, gulose, idose) are modeled with different parameters for the O5–C5–C6–O6 and C4–C5–C6–O6 dihedral angles $^{35}$. Simulations of the remaining 15 steroisomers of glucose have been performed using the same protocol employed for β -d- Glc. We summarized the results in Fig. 5 and Tab. III. In Fig. 5 we report the free energy difference between the $^{1}$C$_{4}$ and $^{4}$C$_{1}$ conformers of α and β -d- pyranoses modeled using the 45a4 force field, along with the theoretical estimates of of Angyal 62 and of Vijayalakshmi and coworkers $^{63}$. Two horizontal dashed lines are also drawn at 0 and 5 kJ/mol (approximatively 2 k b T at room temperature), highlighting the thresholds below which the inverted chair population becomes greater than the chair one, and below which the inverted chair population becomes noticeable, respectively. In Tab. III, free energy differences and populations for the complete α and β series are listed. Beside those of $^{1}$C$_{4}$ , the free energy difference and population of the next leading conformer are also reported, as well as the location on the ( θ, φ ) plane (and the closest recognizable conformer) of the first transitions next to $^{4}$C$_{1}$ . Concerning the population of the leading next conformer, the values reported were calculated on the θ ∈ [ π/ 3 , 2 π/ 3] region. This choice takes into account all other local minima present along the equatorial line, but their free energy is always so large (as it has been seen for β -d- Glc), that this approximation doesn’t change substantially the population of the next leading conformer. The differences between the theoretical estimates and the simulation results obtained using the gromos 45a4 force field are striking. First of all, none of the 16 sugars investigated presents a chair/inverted chair free energy difference in quantitative agreement with the theory, as differences are usually larger than 5 kJ/mol, and in many cases even larger than 10 kJ/mol. More importantly, many of these values are in marked qualitative disagreement not only with the theoretical results, but also with experimental evidence. In fact, α -d- Glc, α -d- Gal, α -d- Man, β -d- Gal and β -d- Man present an inverted chair free energy which 16