Carbohydrates have been increasingly associated with several biological events, from immune defense and cellular growth, to influencing several properties of proteins, as folding and stability. Such a broad range of functions is possibly related to their great structural diversity, as carbohydrates can be branched and linked through different atoms of their monomeric units. A proper understanding of carbohydrate roles over biological systems requires an appropriate characterization, at the atomic level, of their conformation and dynamics. In this scenario, atomistic molecular dynamics simulations emerge as a powerful tool, providing data about carbohydrates typically inaccessible to experimental methods, with both atomic and temporal resolution. As the continuum upgrading of molecular dynamics simulation force fields is crucial to meet the new structures and the emerging glycobiology demands, the present work intends to improve and expand the GROMOS force field for aldohexopyranoses and glycoproteins. This work employed ab initio calculations, metadynamics and unbiased molecular dynamics simulations, using the GROMACS simulation suite, and GROMOS 54A7 force field for the protein moieties of glycoproteins. A fitting of MM to QM torsional profiles was initially performed for dihedrals comprising the N-, O-, S-, C- and P-glycosidic linkages of glycoproteins. Such parameters were shown as capable to properly describe monosaccharides ring puckering parameters, and glycosidic linkage geometries. The proposed parameter modifications have shown a significant improvement over previous versions of GROMOS and GLYCAM06 force fields. The effects of glycosylation over the studied protein structures were also adequately reproduced. Moreover, a set of NMR-derived protein-carbohydrate and carbohydrate-carbohydrate NOE signals were also properly accessed. Thus, the so called GROMOS 53A6GLYC force field is capable to adequately describing carbohydrates conformation and dynamics, while retaining full compatibility with GROMOS parameters for other classes of biomolecules.

GROMOS 53A6<sub>GLYC</sub> force field for aldohexopyranoses and glycoproteins

248th National Meeting (2014)

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GROMOS 53A6GLYC force field for aldohexopyranoses and glycoproteins

GROMOS 53A6_GLYC force field for aldohexopyranoses and glycoproteins