Glycans modulate the adsorption of RBD Glycoproteins on polarizable surfaces

The complex interplay between glycans and protein conformational dynamics during adsorption onto polarizable surfaces opens several routes to exploring the glycans potential as molecular interactions modulators. Molecular simulations are able to dissect the interactions of Receptor Binding Domain (RBD) glycoproteins for different SARS-CoV-2 variants of concern (VoC), in both open and closed conformations, with polarizable planar interfaces. Advanced analysis projected on 2D revealed distinct adsorption mechanisms depending on the initial loci of the glycan within the protein wall. Hydrophobic surfaces facilitated stable adsorption for both RBD conformations. Conversely, hydrophilic surfaces exhibited reduced adsorption, particularly for the closed-RBD, where glycans predominantly formed hydrogen bonds. Glycans significantly modulated closed-RBD adsorption, either enhancing it by permanent tethering or impeding it depending on the two initial conformations and protein mutations (omicron). Results for the individual RBDs are shown to be consistent with simulations for the complete S1 spike glycoprotein. Our findings unveil novel glycan-mediated adsorption phenomena and provide fundamental insights into glycoprotein-surface interactions, paving the way for understanding glycan roles in protein aggregation and recognition at polarizable biological interfaces.