Breaking Down the\nBottlebrush: Atomically Detailed\nStructural Dynamics of Mucins

Mucins, the biomolecular\ncomponents of mucus, are glycoproteins\nthat form a thick physical barrier at all tissue–air interfaces,\nforming a first line of defense against pathogens. Structural features\nof mucins and their interactions with other biomolecules remain largely\nunexplored due to the challenges associated with their high-resolution\ncharacterization. Combining limited mass spectrometry glycomics and\nprotein sequencing data, we present all-atom, explicitly solvated\nmolecular dynamics simulations of a major respiratory mucin, MUC5B.\nWe detail key forces and degrees of freedom imposed by the extensive <i>O</i>-glycosylation, which imbue the canonically observed bottlebrush-like\nstructures to these otherwise intrinsically disordered protein backbones.\nWe compare our simulation results to static structures observed in\nrecent scanning tunneling microscopy experiments as well as other\npublished experimental efforts. Our work represents the demonstration\nof a workflow applied to a mucin example, which we hope will be employed\nby other groups to investigate the dynamics and interactions of other\nmucins, which can inform on structural details currently inaccessible\nto experimental techniques.