Conformation and Energy of Saccharides: Accounting for the Presence of Water in the QM Calculations

The conformational, tautomeric, anomeric and epimeric equilibria of carbohydrates play an important role in their biological functioning and chemical reactivity. In most of the cases the associated processes occur in aqueous solution, therefore computing the properties of hydrated systems is important to predict real behavior of molecules. 

Accounting for the presence of explicit solvent is usually out of the question in the case of the high-level, quantum-mechanical (QM) calculations. However, there are a large number of evidences that implicit solvation models are often insufficient to obtain accurate results related to the carbohydrate conformational properties. Here we describe the ‘hybrid’ computational approach that combines the advantages of classical molecular dynamics simulations (i.e. the presence of explicit solvent) and QM calculations (accuracy of the associated potentials of interactions within the system) [1]. 

The proposed approach is a two-step procedure. In the first step, the structural information is obtained from molecular dynamics simulations performed within the classical, carbohydrate-dedicated force field and in the presence of explicit solvent. Then, this information and associated statistics are used in the subsequent, QM calculations. Such protocol eliminates the contribution of the low-energy conformers which are not very abundant in physical systems due to the influence of the solvent (i.e. mainly the conformers with intramolecular hydrogen bonds). At the same time, the number of representative structures remains relatively low which allows for efficient QM calculations.

We have applied this computational protocol to study the conformational, tautomeric, anomeric and epimeric equilibria features of selected D-aldo- and D-ketohexoses in aqueous solution [1,2]. The comparison with the experimental data revealed satisfactory agreement of the theoretical calculations with the available data. The related calculations provided also several insights into the properties of carbohydrates that have not been previously reported (e.g. quantitative determination of the ring-inversion energies in oligomeric chains or the correlation of the tautomeric preferences of monosaccharides with the conformational energies of the favorable pyranose ring conformer).