Multiscale Modelling Approaches To Understanding The Structure - Dynamics-function Relationships Of Protein Glycosylation

Glycosylation is one of the most common post-translational modifications. Despite recent developments in experimental methods such as X-ray crystallography, NMR and cryo-electron microscopy, it remains challenging to study the structures and dynamics of glycans because of their inherent flexibility and their chemical heterogeneity. The existing gaps in our knowledge regarding glycan conformational dynamics could be filled by molecular simulation approaches if the biophysical and physicochemical properties of the glycans are accurately represented by the underlying forcefield, which describes the energies and forces within the system of interest. In this work, we have extended an existing pseudo-atomic coarse-grained forcefield towards the simulation of glycans. Parameters for the physiologically most relevant N-glycans and glycosaminoglycans were tuned to ensure accurate adoption of local/global properties, aggregative behavior and binding affinities. Later, the developed models were used for investigating the role of glycan roles in the oligomerization of heavily glycosylated epidermal growth factor receptor.

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