Performance of the SCC-DFTB Model for Description of Five-Membered Ring Carbohydrate Conformations: Comparison to Force Fields, High-Level Electronic Structure Methods, and Experiment

The solution conformations of biologically important mono- and di-alpha-D-arabinofuranosides were investigated using the dispersion-corrected self-consistent charge density functional tight binding (SCC-DFTB) and the AMBER/GLYCAM models. Simulations were performed using both long dynamics and umbrella sampling simulations. Angular distributions about the exocyclic C-C bonds and puckering distributions of the rings obtained from the SCC-DFTB model were quite different from those obtained with the AMBER/GLYCAM approach. The joint probability distribution of rotamer and ring puckering parameters reveals further discrepancies, while both methods predict weak correlation between exocyclic torsions and ring puckering. To assess the reliability of the simulations, ensemble-averaged vicinal proton proton coupling constants ((3)J(H,H)) were calculated and compared directly to experimental NMR coupling constants. It is found that the (3)J(H,H) values obtained from the AMBER/GLYCAM simulations agree with experiment, while those obtained from the SCC-DFTB method, in most cases, differ from experimental (3)J(H,H) values. Potential energy surfaces (PES) along the exocyclic torsion obtained from ab initio and DFT calculations differ significantly from those obtained with the SCC-DFTB method. This study establishes that a high-quality all-atom force field would be more suitable than one of the superior semiempirical methods, SCC-DFTB, for investigation of rotamer populations and ring puckering in floppy ring systems such as furanosides.