C. A. G. Haasnoot

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

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. ...

Carbohydrates and drug discovery — the role of computer simulation

Recent advances in the molecular modelling of carbohydrates have brought this technique to a level comparable with that of protein and nucleic acid simulations. After a brief introduction to the techniques used in the computer simulation of carbohydrates and carbohydrate interactions, an overview of applications in the field of carbohydrate-related drug discovery is presented.

Conformational analysis of the trimannose Manα(1 → 2)[Manα(1 → 6)]Manβ using the CHEAT95 force field; evaluation of the additivity principle

Abstract A molecular mechanics study using the CHARMm-based CHEAT95 force field was carried out for the trimannopyranose Manα(1 → 2)[Manα(1 → 6)]Manβ and its two corresponding dimannoses Manα(1 → 2)Man and Manα(1 → 6)Man. Full grid searches of the glycosidic angles were carried out. The dimannopyranoses were simulated effectively using the CHEAT95 force field and the results generally agreed with published experimental and calculated geometrical and energetical data. Analysis of the full grid search of the trimannose shows that the additivity principle leads to incomplete sets of low-energy minima.