CheSweet: first steps into validating and determining glycan structures

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

Ciudad Autónoma de Buenos Aires

Simposio; Primer simposio argentino de glicobilogia "GlycoAR 2014"; 2014

Fundación Instituo Leloir

Over the last several years, we have focused our efforts on developing computational tools, such as the CheShift-2 server, for automated validation of X-ray and NMR-determined protein structures, provided that the observed 13Ca and/or 13Cb chemical shifts are available. However, more than 50% of known proteins are glycoproteins, although only 3.5% of the proteins deposited in the Protein Data Bank are actually glycosylated. There are many reasons to account for the paucity of glycoproteins in the PDB; among others, the following: carbohydrates are very flexible molecules and, therefore, often do not yield sufficient electron density, in X-ray diffraction experiments, to resolve their three-dimensional structure. In addition, about 30% of the PDB-deposited carbohydrate entries contain errors. Hence, there is a great need for accurate and fast validation methods to detect flaws in protein/glycan structures, at the residue/disaccharide level. Our long-term goal is to develop a computational method with which to validate and determine glycan, glycoprotein and other glycoconjugated structures. This method will be based on the computation of 13C chemical shifts, at the DFT-level of theory, as a function of the torsional angles in disaccharides. We have named such a method CheSweet and here we discuss our first steps towards its development and implementation.