Modelling of β-d-glucopyranose ring distortion in different force fields: a metadynamics study Original Research Article

Modelling of carbohydrate conformations is a challenging task for force field developers. Three carbohydrate force fields, namely GLYCAM06, GROMOS 45a4 and OPLS were evaluated. Free energies of different ring conformations of β-d-glucopyranose were calculated using metadynamics in vacuum as well as in explicitly modelled water. All three force fields model the 4C1 conformation as the most stable by at least 6 kJ/mol, as compared to other conformations. Interconversion from the 4C1 to any other conformation is associated with a barrier of no lower than 26 kJ/mol. The free energy surface calculated in the GLYCAM06 force field is in remarkably good agreement with the recent Car-Parrinello metadynamics study. The effect of a water environment is relatively low and analogous in all tested force fields. Namely, the presence of water stabilizes the upper-left (3,OB) versus bottom-right (B3,O) area of Stoddard’s plot, relative to the situation in vacuum. Comparison of free and potential surfaces is also provided for vacuum calculations.