Ab Initio Modeling of Glycosyl Torsions and Anomeric Effects in a Model Carbohydrate: 2-Ethoxy Tetrahydropyran

• Published in: Biophysical journal Vol. 93; no. 1; pp. 1 - 10
• Main Authors: Woodcock, H. Lee, Moran, Damian, Pastor, Richard W., MacKerell, Alexander D., Brooks, Bernard R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2007; Biophysical Society; The Biophysical Society
• Subjects: Biophysical Theory and Modeling; Biophysics; Carbohydrates; Computer Simulation; Dimerization; Glycosylation; Models, Chemical; Models, Molecular; Molecular Conformation; Pyrans - chemistry; Surface Properties
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.106.099986

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 Δ E = E equatorial − E axial = 1.42 kcal/mol. When corrected for solvent (by the IEFPCM model), zero-point vibrations and entropy, Δ G 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 Δ E 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 Δ E by ∼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.