Conformational Preferences of Glycans from the Use of 13C Chemical Shifts

GARAY PABLO G.; MARTIN OSVALDO O.; VILLEGAS MYRIAM E.; SCHERAGA HAROLD A.; VILA JORGE A.

San Javier Tucumán

Congreso; SAB 2012: XLI Reunión Anual de la Sociedad Argentina de Biofísica; 2012

Sociedad Argentina de Biofísica

The addition of oligosaccharides to proteins is a significant post-translational modification that modulates protein structure and function. Glycans are vital for development in all eukaryotes and are profoundly connected to a large number of human diseases, ranging from glycan genetic diseases to auto-immune disorders and cancer. Knowledge of the three-dimensional structures of the carbohydrate molecules is indispensable for a full understanding of the molecular processes in which carbohydrates are involved, such as protein glycosylation or protein?carbohydrate interactions. The Protein Data Bank (PDB) is a valuable resource for three-dimensional structural information on glycoproteins and protein?carbohydrate complexes. Unfortunately, many carbohydrate moieties in the PDB contain inconsistencies or errors and, hence, the need for accurate and fast validation methods to detect flaws in glycan structures appears to be crucial. Because 13C is ubiquitous in glycans, this makes the 13C nucleus an attractive candidate for computation of theoretical chemical shifts at the quantum chemical level of theory in order to determine, refine and validate glycan structures. For an accurate computation of the 13C chemical shifts in glycans, at the DFT level of theory, it is very important to determine the influence of all factors that affect the computation of the 13C-shielding, among them the density functional model and the basis set adopted. Consequently ten density functionals and six basis sets will be tested here for their ability to reproduce 13C chemical shifts in glycans accurately.