Monte Carlo-based searching as a tool to study carbohydrate structure

Abstract

A torsion angle-based Monte Carlo searching routine was developed and applied to several carbohydrate modeling problems. The routine was developed as a Unix shell script that calls several programs, which allows it to be interfaced with multiple potential functions and various utilities for evaluating conformers. In its current form, the program operates with several versions of the MM3 and MM4 molecular mechanics programs and has a module to calculate hydrogen–hydrogen coupling constants. The routine was used to study the low-energy exo-cyclic substituents of β- d-glucopyranose and the conformers of d-glucaramide, both of which had been previously studied with MM3 by full conformational searches. For these molecules, the program found all previously reported low-energy structures. The routine was also used to find favorable conformers of 2,3,4,5-tetra- O-acetyl- N, N′-dimethyl- d-glucaramide and d-glucitol, the latter of which is believed to have many low-energy forms. Finally, the technique was used to study the inter-ring conformations of β-gentiobiose, a β-(1→6)-linked disaccharide of d-glucopyranose. The program easily found conformers in the 10 previously identified low-energy regions for this disaccharide. In 6 of the 10 local regions, the same previously identified low-energy structures were found. In the remaining four regions, the search identified structures with slightly lower energies than those previously reported. The approach should be useful for extending modeling studies on acyclic monosaccharides and possibly oligosaccharides.