|Willett, Julious - Jl|
Submitted to: Carbohydrate Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/7/2009
Publication Date: 1/4/2010
Citation: Schnupf, U., Willett, J.L., Momany, F.A. 2010. DFTMD Studies of Glucose and Epimers: Anomeric Ratios Rotamer Populations, and Hydration Energies. Carbohydrate Research. 345(1):503-511. Interpretive Summary: We have carried out this computational study to better understand the flexibility, energy, and vibrational organization of glucose and its seven cyclic epimers. Understanding physical parameters such as anomeric ratios and rotamer populations will help us form new and more efficient design methods for 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 like materials and design of copolymers. Glucose is the basic monomer unit of starch and cellulose polymers, and is an important component in human health. Previous computational studies using advanced electronic structure theory have produced structures, energies, and vibrational frequencies of these model carbohydrates. In this work we extend our studies of all the epimers to more realistic room temperature dynamic 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 for each molecule allows us to cover a vast array of possible conformational space which can then be compared to experimental anomeric and rotamer data.
Technical Abstract: Results are presented from density functional molecular dynamics (DFTMD) simulations, based on constant energy dynamics, of glucose and its cyclic form of 6-carbon epimers. Both in vacuo and an implicit solvent method (COSMO) were examined including simulations of all low energy conformations of each molecule. Analysis of the DFTMD results includes: energies averaged over the simulation time, calculated anomeric ratios, hydroxyl and hydroxymethyl rotamer populations, and hydration energies. Hydrogen bonding networks persistence times were examined and the effects of solvation on rotamer populations described. Anomeric ratios calculated from energy optimization of an ensemble of low energy conformers are compared to those obtained from ensemble averages from molecular dynamics, with dynamics simulations giving populations in best agreement with experimental anomeric ratios. In vacuo ensemble results were not in agreement with experimental anomeric ratios or hydroxymethyl populations producing in some cases, reversal of the a:Beta ratios. The difficulty in obtaining correct a:Beta ratios increases with number of axial groups; the mono-axial epimers being best represented, epimers with two axial groups being more difficult, and the epimers with three axial hydroxyl groups being most difficult to analyze, the result of a large number of very strong hydrogen bonding networks which form the ensemble of low energy conformations in the multi-axial structures.