A CHARMM BASED FORCE-FIELD FOR CARBOHYDRATES USING THE CHEAT APPROACH- CARBOHYDRATE HYDROXYL-GROUPS REPRESENTED BY EXTENDED ATOMS

Computational studies of carbohydrates that do not consider explicit s olvent molecules suffer from the strong tendency of the carbohydrate p endant 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 averag e effect of intra- and intermolecular hydrogen bonding is introduced i nto 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 Extende d AToms) for the resulting force field. As a training set for the para metrisation of CHEAT we used ethylene glycol, 10 cyclohexanols, 5 inos itols, and 12 glycopyranoses for which in total 64 conformational ener gy differences were estimated using a set of steric interaction energi es between hydroxyl and/or methyl groups on six-membered ring compound s as derived by Angyal (Angew. Chem., 81, 172-182, (1969)). The root-m ean-square deviation between the estimated energy differences and the corresponding values obtained by our CHEAT approach amounts to 0.37 kc al/mol (n = 64). The CHEAT approach, which is claimed to calculate aqu eous state compatible energetical and conformational properties of car bohydrates, is computationally very efficient and facilitates the calc ulation of nanosecond range MD trajectories as well as systematic conf ormational searches of oligosaccharides.