Aqueous-Phase Conformations of Lactose, Maltose, and Sucrose and the Assessment of Low-Cost DFT Methods with the DSCONF Set of Conformers for the Three Disaccharides

In the present study, we have examined
a range of quantum chemistry
methods for the calculation of conformers for lactose, maltose, and
sucrose. We find that the DSD-PBE-P86/aug′-cc-pVTZ//B3-LYP-D3BJ/6-311+G­(2d,p)
protocol yields good relative energies in comparison with reference
CCSD­(T)/CBS//B3-LYP-D3BJ/maug-cc-pVTZ values. We have surveyed a total
of ∼550 conformers for the three disaccharides with the chosen
DSD-PBE-P86 method in conjunction with continuum aqueous solvation.
In each case, the lowest free energy conformer is characterized by
hydrogen bond(s) between the two rings. Another finding is that the
major contributors to the overall variations in aqueous free energies
are the electronic energies and the solvation energies. To facilitate
investigations of larger systems, we have compiled the DSCONF set
of conformers for the three disaccharides, and we have assessed lower
cost methods with this set. We find MS1-D3/6-31+G­(2d,p) to be cost-effective
and accurate for both geometry optimization and the calculation of
relative energies for disaccharides. In addition, we note that MS1-D3
has previously been found to yield good relative energies for the
WATER27 set of water clusters. We thus deem this method to be appropriate
for the study of saccharide conformations in both gas phase and aqueous
solution.