Molecular dynamics simulation of the aqueous solvation of sugars.

Recently, several molecular dynamics simulations of the aqueous solvation of carbohydrates have been reported. These studies represent the first theoretical picture available of the microscopic character of sugar solutions, and may provide explanations of the unusual and complex behavior of this class of molecules in solution. This paper will discuss two MD simulations of D-glucopyranose, including a free energy perturbation calculation of the anomeric free energy difference. Solvation was found to have little effect upon the mean conformational structure of the pyranoid rings, but the presence of solvent significantly affected the motions and orientations of the exocyclic groups. Adjacent functional groups of the sugar rings were found to mutually perturb one another's hydration, depending upon the local stereochemistry, which may prove to play a part in the observed anomeric preferences of the sugars. From a component analysis of the free energy of solvation of the two anomers of D-glucopyranose, it was found that a large solvation term favors the beta anomer, which is the form found to be preferred in aqueous solution.

A revised potential-energy surface for molecular mechanics studies of carbohydrates.

A revised CHARMM-type molecular mechanics potential-energy function has been developed for use in the dynamical simulation of simple carbohydrates in aqueous solution. Atomic charges used in this parameterization were taken to be those previously determined to be appropriate for hydrogen-bonded systems, and the various force-constants were selected by the nonlinear least-squares matching of the calculated normal-mode frequencies and minimum-energy structure to experiment as a function of the parameter set. The new function was found to represent the vibrational spectrum and ring pucker of alpha-D-glucopyranose as well as previously studied potentials, while incorporating the charges necessary for the simulation of condensed phases. Molecular dynamics simulations of the motions of alpha-D-glucopyranose in vacuo in both the 1C4 and 4C1 conformation were conducted, and compared to the results of previous simulations using another potential-energy function. The revised potential function was found to produce a D-glucose molecule less flexible in vacuo than had been previously observed.