Additive effects in the modeling of oligosaccharides with MM3 at high dielectric constants: an approach to the...

The production of an adiabatic map for a di- or trisaccharide requires the generation of many relaxed maps, ideally 59,049 for a disaccharide or 4,782,969 for a trisaccharide composed by hexose residues, due to a combination of exocyclic angle torsions. As the production of this amount of maps is usually ruled out for time considerations, different approaches were exploited. When working at low dielectric constants, starting points originated in cooperative hydrogen bonds through the rings are usually sufficient to produce an adiabatic map, but at higher dielectric constants those circuits are meaningless, and many low-energy conformers appear in each energy well. Herein, different conformations of four disaccharides (beta-4-linked mannobiose, and three galactobioses, linked alpha-(1-->3), alpha-(1-->4), and beta-(1-->4)) and one trisaccharide (beta-4-linked mannotriose) were minimized using mm3 at epsilon = 80, and the difference in energy produced by changes in torsional angles was recorded. A remarkable additive effect was found to occur when the exocyclics were gathered in groupings of two or three neighboring angles. Thus, in most cases, each grouping can be studied separately, and the minimum energy conformers can be predicted without the need of resorting to thousands of calculations. In some cases where two protons of different groups show steric interactions in some specific conformations, small deviations of the additivity were encountered. Anyway, a complex system with many variables can be transformed in one with many fewer variables, thus simplifying further studies. An attempt to calculate the same effect at epsilon = 3 shows that hydrogen bonding and electrostatic interactions make impossible to find those additive effects, thus precluding its utilization at such low dielectric constants.