DFTMD studies of glucose and epimers: anomeric ratios, rotamer populations, and hydration energies

Results are presented from density functional molecular dynamics (DFTMD) simulations, based on constant energy dynamics, of glucose and its cyclic form of 6-carbon epimers. Both in vacuo and an implicit solvent method (COSMO) were examined, including simulations of low-energy conformations of each molecule. Analysis of the DFTMD results includes the following: energies averaged over the simulation time, calculated anomeric ratios, hydroxyl and hydroxymethyl rotamer populations, and hydration energies. Hydrogen-bonding networks persistence times were examined, and the effects of solvation on rotamer populations were described. Anomeric ratios calculated from energy optimization of an ensemble of low-energy conformers are compared to those obtained from ensemble averages from molecular dynamics, with dynamics simulations giving populations in best agreement with experimental anomeric ratios. Ensemble results in vacuo were not in agreement with experimental anomeric ratios or hydroxymethyl populations, producing in some cases reversal of the alpha:beta ratios. The difficulty in obtaining correct alpha:beta ratios increases with the number of axial groups; the mono-axial epimers being best represented, epimers with two axial groups being more difficult, and the epimers with three axial hydroxyl groups being most difficult to analyze, the result of a large number of very strong hydrogen-bonding networks that form the ensemble of low-energy conformations in the multi-axial structures. Published by Elsevier Ltd.