Molecular modeling of agarose helices, leading to the prediction of crystalline allomorphs

Abstract

The neutral polysaccharide agarose is a linear polymer whose idealized structure is made up of alternating residues of a 1 → 3 linked β-D-galactopyranose and 1 → 4 linked 3,6-anhydro-α-L-galactopyranose. Apparently conflicting reports have been published about the nature of the helical structure of agarose in the condense phase. Recent developments in the field of molecular modeling of polysaccharides offer some new opportunities to reexamine the structural basis underlying the formation and stabilization of ordered structures. The conformational spaces available for each disaccharide segments were investigated via molecular dynamics simulations. Then, making use of the available experimental information of the helical symmetry, axial advances, the optimal glycosidic torsion angles were assessed. The search for the lowest energy helix included both left- and right-handed, and both single- and double-helical, models. A further analysis considered all possible arrangements occurring between an agarose chain, in a given conformation, and another chain. Both parallel and antiparallel settings of the chains were evaluated. Unit-cell dimensions as well as lattice symmetry were derived from which intensities of x-ray reflections were calculated. The calculations lead to the prediction of three single-helical structure and one parallel double-helical model; they are all left-handed and the chains pack in an antiparallel way. The predicted crystalline structures compare favorably with available experimental data. Water can occupy 30–45% of the space in the crystal structures, which is in accordance with the gel-forming behavior. The models obtained may reflect the relative arrangements of agarose helices in some of the main allomorphs. They provide some insights into the common structural features and into the differences that accompany the conformational transitions between these allomorphs. © 1998 John Wiley & Sons, Inc. Biopoly 46: 11–29, 1998