Conformational-energy calculations for oligosaccharides: a comparison of methods and a strategy of calculation☆

Abstract A theoretical conformational analysis of dimethoxymethane, 2-methoxytetrahydropyran, cellobiose, and maltose has been performed. The validity of several commonly used classical approaches to conformational energy, assuming non-bonded interactions, torsional terms, and the exo-anomeric contribution, and the MM2CARB method (a modified version of the MM2 force-field program using the Jeffrey-Taylor parameters) was tested against available experimental data or previous quantum-chemical calculations. The MM2CARB method correctly reproduces the energies and the variations in bond lengths and bond angles for conformers of dimethoxymethane and 2-methoxytetrahydropyran. Prediction of the observed conformers with simple potential functions appears to be less satisfactory. In particular, calculations that take into account non-bonded interactions and the exo-anomeric contribution based on dimethoxymethane give predicted energy differences that are 2–3 times higher than the experimental values. The general shapes of the ( Φ , Ψ ) potential-energy surfaces for cellobiose and maltose provided by potential-function calculations suggest the presence of several minima whose energies depend, to a great extent, on the choice of molecular geometry. The MM2CARB-calculated structures of seven cellobiose and five maltose conformers demonstrate clearly the variation of disaccharide geometry with change of conformation around the glycosidic linkage. The relative energies calculated by simple methods differ from MM2CARB energies and indicate that the simple potential-functions methods give only a qualitative estimate of oligosaccharide conformers. Based on these results, we propose a general strategy and two different approaches for the investigation of conformational properties of oligosaccharides.

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