  We present the results of a combined metadynamics-umbrella sampling
investigation of the puckered conformers of pyranoses described using the
gromos 45a4 force field. The free energy landscape of Cremer-Pople puckering
coordinates has been calculated for the whole series of alpha and beta
aldohexoses. We show that the 45a4 force field parameters fail in reproducing
proper free energy differences between chair conformers for many of the
inspected monosaccharides. In the extreme cases of galactose, mannose and
allose, the experimentally non-detectable inverted chair conformers become even
substantially populated. The opposite behavior is observed in the case of
idose, which is the only experimentally known aldohexose that shows equilibrium
between chair and inverted chair. We suggest a modification to the gromos 45a4
parameter set, which improves considerably the accordance of simulation results
with theoretical and experimental estimates of puckering free energies.
