DFT Molecular Dynamics (DFTMD) Simulations of Carbohydrates: I. COSMO Solvated Alpha-maltose

Authors: Momany, Frank; Willett, Julious; Schnupf, Udo

Submitted to: Journal of Molecular Structure (Theochem)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/4/2010
Publication Date: 6/11/2010
Citation: Momany, F.A., Willett, J.L., Schnupf, U. 2010. DFT Molecular Dynamics (DFTMD) Simulations of Carbohydrates: I. COSMO Solvated Alpha-maltose. Journal of Molecular Structure (Theochem).

Interpretive Summary: We have carried out this computational study to better understand the flexibility and structural organization of the building blocks of starch materials. This understanding will help us form new and more efficient design methods for chemical modifications of starch or polymer blends with the potential result that new biodegradable natural polymers with interesting physical properties will be found. These results are important to industries developing new biodegradable materials and to other computational and laboratory scientists working on simulation of starch materials and design of copolymers. Maltose is the basic disaccharide unit of starch polymers, containing one glycosidic bond between two glucose residues. Previous computational studies using advanced electronic structure theory have produced structures and energetic profiles of these model carbohydrates, but only at their geometry optimized forms as if they were at zero Kelvin. In this work we extend our study to more realistic room temperature forms and include the effects of the solvent, water. Molecular dynamics simulations at the quantum mechanics level are difficult and time consuming and only possible because of the advances in computing software and hardware. The advantages of molecular dynamics is that one observes how the molecule moves in solution at room temperature and what structural arrangements or conformations are most probable. Using short bursts of dynamics on many different starting structures allows us to cover a vast array of possible conformational space which can then be compared to the limited experimental data. This information is very difficult to obtain experimentally, where average values of a few parameters are most often the best one can hope for.

Technical Abstract: Density functional molecular dynamics (DFTMD) is carried out on low-energy conformations of alpha-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 “kinks” 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 ~2.15Å 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 O6-H6---O6’ hydrogen bond locked into a glycosidic ‘kink’ structure, allowing the O3-H3 and O2’-H2’ hydroxyl groups between rings to rotate more freely because of the enlarged distances between the groups across the glycosidic bridge.