The O-glycosidic and N-glycosidic linkages are important protein modifications in which oligosaccharides are linked to Ser/Thr and Asn residues, respectively. These linkages involve the anomeric carbon of the carbohydrates and the alcoholic side groups of Ser/Thr or the amide group of the Asn side chain. The O- and N-glycosidic linkages are ubiquitous in biological systems including glycoproteins like mucin, epidermal growth factor (EGF), domains of different serum proteins and Notch receptors, among many others, where the presence of the carbohydrate moiety is important for the biological functions of the proteins.In an ongoing effort to develop the CHARMM all-atom additive carbohydrate force field we present and validate parameters that will enable the modeling of the O- and N-glycosidic linkages. The parameters represent an extension of the existing CHARMM carbohydrate and protein force fields.1-2 The target data for the optimization process included quantum mechanical (QM) potential energy scans of the torsions involved in the glycosidic linkages. Force field validations included comparison of the intermolecular geometries for the QM and crystal studies, comparison of the crystalline unit-cell properties and experimental NMR J-coupling constants. The optimized parameters were then used to rationalize the differences between the Ser and Thr O-glycan linkages using a Hamiltonian Replica Exchange protocol (HREX). We found that the solvent structure closely governs the linkage geometry due to the involvement of bridged waters between the carbohydrate and protein regions.(1) Guvench, O.; Hatcher, E. R.; Venable, R. M.; Pastor, R. W.; Mackerell, A. D. J. Chem. Theory Comput 2009, 5, 2353-2370.(2) Guvench, O.; Greene, S. N.; Kamath, G.; Brady, J. W.; Venable, R. M.; Pastor, R. W.; Mackerell, A. D. J. Comput. Chem. 2008, 29, 2543-64.