QM/MM simulations of carbohydrates

Hybrid quantum mechanical (QM)/molecular mechanical (MM) molecular dynamics simulations were used to investigate disaccharide conformation in aqueous solution. In vacuo and aqueous solution conformational free energy surfaces were constructed from potential of mean force calculations, using weighted histogram analysis of combined QM/MM molecular dynamics simulations of 8.5 ns and 13.5 ns respectively. Calculations indicated the presence of direct and water-bridged intersaccharide hydrogen bonds, the latter consistent with a broad range of phi psi space. To improve the accuracy of the description of carbohydrates by semi-empirical QM methods, we also detail our work on reparameterization of the PM3 Hamiltonian. This is based on fitting to 1,2-ethanediol structures and energies. Application of the resulting model, PM3CARB-1, to modeling of glucose is discussed. Improvement in energetic ranking of C-4(1) and C-1(4) conformations was found. QM/MM dynamics simulations of a disaccharide using PM3CARB-1 did not exhibit transitions from C-4(1) to C-1(4) structures. (c) 2006 American Chemical Society