GROMOS96 43a1 performance in predicting oligosaccharide conformational ensembles within glycoproteins

Abstract In previous work [Pol-Fachin, L.; Fernandes, C. L.; Verli, H.; Carbohydr. Res. 2009 , 344 , 491–500], we had demonstrated that GROMOS96 43a1 force field and Lowdin HF/6-31G∗∗-derived atomic charges, adequately represent a glycoprotein’s conformational ensemble in aqueous solutions, taking as the starting geometries NMR-determined structures. Based on such data, the present work intends to evaluate the use of the main solution conformations of isolated disaccharides, to build the carbohydrate moiety of glycoproteins, for which no previous experimental information is available. The observed results suggested that the entire glycoprotein scaffold appears unable to promote major modifications in the conformational behavior of glycosidic linkages. Additionally, when compared to energy contour plots, the results support the use of solution ensembles, to refine vacuum conformations of carbohydrate databases in the assembling of glycoproteins 3D structures. Finally, such approach is applied to build a full glycosylated model for COX-1 and COX-2 enzymes.