Calculation of the Ramachandran potential of mean force for a disaccharide in aqueous solution

Molecular dynamics simulations employing adaptive umbrella sampling have been used to calculate the Ramachandran conformational potential of mean force in aqueous (TIP3P) solution for the alpha(1-->4)-linked dimer of D-xylopyranose (4-O-alpha-D-xylopyranosyl-alpha-D-xylopyranose), a pentose analogue of malto se and a useful general model for the effects of solvent structuring upon biopolymer hydration. The vacuum adiabatic energy map for this molecule closely resembles that for maltose, but the solution pmf is quite different, with one of the principal vacuum minima almost completely disappearing in solution and with the global minimum-energy conformation being a new minimum which does not occur at all on the vacuum surface. This conformation is apparently stabilized by a water molecule which hydrogen bonds to a hydroxyl group on each ring, bridging between the two rings. The new conformation also places the two hydrophobic methylene groups almost in van der Waals contact, reducing their exposed surface area. Unfortunately, the results reaffirm the dependence of hydration effects upon the specific details of each molecule's chemical structure, making the application of simple general models for hydration more difficult.