A CHARMm Based Force Field for Carbohydrates Using the CHEAT Approach: Carbohydrate Hydroxyl Groups Represented by Extended Atoms

Abstract

Abstract Computational studies of carbohydrates that do not consider explicit solvent molecules suffer from the strong tendency of the carbohydrate pendant hydroxyl groups to form intramolecular hydrogen bonds that are unlikely to be present in protic media. In this paper a novel approach towards molecular modelling of carbohydrates is described. The average effect of intra- and intermolecular hydrogen bonding is introduced into the potential energy function by adding a new (extended) atom type representing a carbohydrate hydroxyl group to the CHARMm force field; we coin the name CHEAT (Carbohydrate Hydroxyls represented by Extended AToms) for the resulting force field. As a training set for the parametrisation of CHEAT we used ethylene glycol, 10 cyclohexanols, 5 inositols, and 12 glycopyranoses for which in total 64 conformational energy differences were estimated using a set of steric interaction energies between hydroxyl and/or methyl groups on six-membered ring compounds as derived by Angyal (Angew. Chem., 8, 172-182, (1969)). The root-mean-square deviation between the estimated energy differences and the corresponding values obtained by our CHEAT approach amounts to 0.37 kcal/mol (n = 64). The CHEAT approach, which is claimed to calculate aqueous state compatible energetical and conformational properties of carbohydrates, is computationally very efficient and facilitates the calculation of nanosecond range MD trajectories as well as systematic conformational searches of oligosaccharides.