Conformational Analysis of Arabinofuranosides: Prediction of (3)JH,H Using MD Simulations with DFT-Derived Spin-Spin Coupling Profiles.

A molecular dynamics (MD) investigation on a series of oligo-α-arabinofuranosides (1-8) using the AMBER force field and the GLYCAM carbohydrate parameter set is reported. The validation of the method was carried out by direct comparison of experimental vicinal proton-proton coupling constants ((3)JH,H) with those obtained by using an empirically determined Karplus equation and density functional theory (DFT)-derived relationships specifically tailored for α-arabinofuranosyl systems. A simple code was developed to implement the determination of (3)JH,H by applying these relationships to the probability distributions of rotamers and ring conformations displayed by the simulations. The empirical Karplus relationship and the DFT-derived equations yielded, in most cases, the same trend as experiment for intra-ring (3)JH,H values. This direct comparison circumvents additional sources of errors that may arise from the assumptions introduced by the deconvolution procedures often used to calculate population of rotamers and ring conformations from experimental (3)JH,H.