title: Ab initio modeling of glycosyl torsions and anomeric effects in a model carbohydrate: 2-ethoxy tetrahydropyran.
abstract: A range of ab initio calculations were carried out on the axial and equatorial anomers of the model carbohydrate 2-ethoxy tetrahydropyran to evaluate the level of theory required to accurately evaluate the glycosyl dihedral angle and the anomeric ratio. Vacuum CCSD(T)/CBS extrapolations at the global minimum yield DeltaE = E(equatorial) - E(axial) = 1.42 kcal/mol. When corrected for solvent (by the IEFPCM model), zero-point vibrations and entropy, DeltaG(298) = 0.49 kcal/mol, in excellent agreement with the experimental value of 0.47 +/- 0.3 kcal/mol. A new additivity scheme, the layered composite method (LCM), yields DeltaE to within 0.1 kcal/mol of the CCSD(T)/CBS result at a fraction of the computer requirements. Anomeric ratios and one-dimensional torsional surfaces generated by LCM and the even more efficient MP2/cc-pVTZ level of theory are in excellent agreement, indicating that the latter is suitable for force-field parameterization of carbohydrates. Hartree-Fock and density functional theory differ from CCSD(T)/CBS for DeltaE by approximately 1 kcal/mol; they show similar deviations in torsional surfaces evaluated from LCM. A comparison of vacuum and solvent-corrected one- and two-dimensional torsional surfaces indicates the equatorial form of 2-ethoxy tetrahydropyran is more sensitive to solvent than the axial.
authors.affiliation: Laboratory of Computational Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. hlwood@nih.gov
authors.forename: H Lee
authors.initials: HL
authors.lastname: Woodcock
authors.forename: Damian
authors.initials: D
authors.lastname: Moran
authors.forename: Richard W
authors.initials: RW
authors.lastname: Pastor
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brooks
mesh_terms: D003198:Computer Simulation; D019281:Dimerization; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011714:Pyrans / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D011714:Pyrans