Conformational behavior of hyaluronan in relation to its physical properties as probed by molecular modeling

Hyaluronan (HA) is a linear charged polysaccharide whose structure is made up of repeating disaccharide units. Apparently conflicting reports have bee n published about the nature of the helical structure of HA in the solid st ate. Recent developments in the field of molecular modeling of polysacchari des offer new opportunities to reexamine the structural basis underlying th e formation and stabilization of ordered structures and their interactions with counterions. The conformational spaces available and the low energy co nformations for the disaccharide, trisaccharide, and tetrasaccharide segmen ts of HA were investigated via molecular mechanics calculations using the M M3 force field. First, the results were used to access the configurational statistics of the corresponding polysaccharide. A disordered chain having a persistence length of 75 Angstrom at 25 degrees C is predicted. Then, the exploration of the stable ordered forms of HA led to numerous helical confo rmations, both left- and right-handed, having comparable energies. Several of these conformations correspond to the experimentally observed ones and i llustrate the versatility of the polysaccharide. The double stranded helica l forms have also been explored and theoretical structures have been compar ed to experimentally derived ones.