Additive empirical force field for hexopyranose monosaccharides

Abstract

We present an all‐atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose. The model is developed to be consistent with the CHARMM all‐atom biomolecular force fields, and the same parameters are used for all diastereomers, including both the α‐ and β‐anomers of each monosaccharide. The force field is developed in a hierarchical manner and reproduces the gas‐phase and condensed‐phase properties of small‐molecule model compounds corresponding to fragments of pyranose monosaccharides. The resultant parameters are transferred to the full pyranose monosaccharides, and additional parameter development is done to achieve a complete hexopyranose monosaccharide force field. Parametrization target data include vibrational frequencies, crystal geometries, solute–water interaction energies, molecular volumes, heats of vaporization, and conformational energies, including those for over 1800 monosaccharide conformations at the MP2/cc‐pVTZ//MP2/6‐31G(d) level of theory. Although not targeted during parametrization, free energies of aqueous solvation for the model compounds compare favorably with experimental values. Also well‐reproduced are monosaccharide crystal unit cell dimensions and ring pucker, densities of concentrated aqueous glucose systems, and the thermodynamic and dynamic properties of the exocyclic torsion in dilute aqueous systems. The new parameter set expands the CHARMM additive force field to allow for simulation of heterogeneous systems that include hexopyranose monosaccharides in addition to proteins, nucleic acids, and lipids. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008