DFT molecular dynamics (DFTMD) simulations of carbohydrates: COSMO solvated α-maltose

Density functional molecular dynamics (DFTMD) is carried out on low-energy conformations of α-maltose. Finite temperature molecular dynamics trajectories are generated with forces obtained from B3LYP/6-31+G∗ electronic structure calculations. The implicit solvent method COSMO is applied to simulate the solution environment. Each simulation is carried out for ∼5 ps, starting from low-energy optimized geometries, including different hydroxymethyl rotamers and hydroxyl clockwise, 'c', and counterclockwise, 'r', orientations. The gg′-gg-r solvated form is of lowest relative energy by ∼0.6 kcal/mol relative to the solvated gg′-gg-c form, the latter conformation tending to converge to the 'r' form during dynamics. Conformational transitions and conformers residing as 'kink' forms were observed during vacuum runs. In one case, the syn gt'-gt-r + COSMO conformer moved during dynamics into a 'kink' conformation, remaining there for most of the 5 ps simulation. However, when this same conformer was started from a minimum energy 'kink' form, it rapidly reverted into the normal syn conformation in which the H1′⋯H4 hydrogen atoms across the glycosidic bond were ∼2.15 Å on average. Other solvated structures showed a perfunctory preference for the 'kink' conformation during dynamics, even though in previous optimization studies the 'kink' conformations were of higher energy than the syn conformers. Similarly, 'band-flip' conformational studies showed that the 'c' and 'r' forms differed, 'c' undergoing transitions to the syn form, the 'r' form staying in the band-flip conformation over the 5 ps simulation. The trend for the 'r' conformers to be more stable than the 'c' conformers when fully solvated, appears to confirm optimization studies, although transitions to stable partial 'c' forms produces some confusing conformational effects. For example, in one case a hydroxymethyl O6H⋯O6′ hydrogen bond locked into a glycosidic 'kink' structure, allowing the O3H and O2′H' hydroxyl groups between rings to rotate more freely because of the enlarged distances between the groups across the glycosidic bridge.