title: Metadynamics modelling of the solvent effect on primary hydroxyl rotamer equilibria in hexopyranosides.
abstract: Accurate modelling of rotamer equilibria for the primary hydroxyl groups of monosaccharides continues to be a great challenge of computational glycochemistry. The metadynamics technique was applied to study the conformational free energy surfaces of methyl alpha-D-glucopyranoside and methyl alpha-D-galactopyranoside, employing the GLYCAM06 force field. For both molecules, seven to eight conformational free-energy minima, differing in the omega (O-5-C-5-C-6-O-6) and chi (C-3-C-4-O-4-HO-4) dihedral angles, were identified in vacuum or in a water environment. The calculated rotamer equilibrium of the primary hydroxyl group is significantly different in vacuum than in water. The major effect of a water environment is the destabilisation of a hydrogen bond between O-4-HO-4 and O-6-HO-6 groups. It was possible to calculate the free-energy differences of individual rotamers with an accuracy of better than 2 kJ/mol. The calculated gg, gt and tg rotamer populations in water are in close agreement with experimental measurements, and therefore support the theoretical background of metadynamics.
authors.affiliation: Department of Biochemistry and Microbiology, Institute of Chemical Technology in Prague, Technická 3, 166 28 Prague 6, Czech Republic. chemspiw@savba.sk
authors.forename: Vojtech
authors.initials: V
authors.lastname: Spiwok
authors.forename: Igor
authors.initials: I
authors.lastname: Tvaroska
mesh_terms: D003198:Computer Simulation; D005690:Galactose / Q000031:analogs & derivatives / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry*; D008757:Methylglucosides / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D006027:Glycosides; D008757:Methylglucosides; D012997:Solvents; C469243:methyl-galactopyranoside; C027020:methylglucoside; D005690:Galactose