Various post translational modifications like hyper phosphorylation, O-GlycNAcylation, and acetylation have been attributed to induce the abnormal folding in tau protein. Recent in vitro studies revealed the possible involvement of N–glycosylation of tau protein in the abnormal folding and tau aggregation. Hence in this study, we performed microsecond long all atom molecular dynamics simulation to gain insights into the effects of N-glycosylation on Asn-359residue which forms part of the microtubule binding region. Trajectory analysis of the stimulations coupled with essential dynamics and free energy landscape analysis suggested that tau, in its N-glycosylated form tend to exist in a largely folded conformation having high beta sheet propensity as compared to unmodified tau which exists in a large extended form with very less beta sheet propensity. Residue interaction network analysis of the lowest energy conformations further revealed that Phe378 and Lys353 are the functionally important residues in the peptide which helped in initiating the folding process and Phe378, Lys347&Lys370 helped maintaining the stability of the protein in the folded state.
N-glycosylation induced changes in tau protein dynamics reveal its role in tau misfolding and aggregation: A microsecond long molecular dynamics study
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