A molecular mechanics‐NMR pseudoenergy approach to the solution conformation of glycolipids

We present here a protocol for the determination of oligosaccharide solution conformation from a combination of molecular mechanics calculations and NMR distance constraints treated as pseudoenergies. As an illustration of our methodology we have chosen the determination of the solution conformation of the tetrasaccharide headgroup of the glycolipid globoside. In order to test the ability of our methodology to avoid becoming trapped in local minima, we have chosen three starting structures, well displaced from one another in conformational space. The structures obtained upon convergence of the calculations with distance constraint pseudoenergies were quite similar to one another. For two of the three glycosidic linkages in globoside, the results from the calculations were virtually identical for each of the three starting structures. We also apply our protocol to a model which allows for the existence of multiple conformers in an effort to explore the possibility of conformational flexibility in the oligosaccharide headgroup of globoside.