Impact of Glycosylation of Apolipoprotein D on Its Interaction with Gold Nanoparticles: Insights from Molecular Dynamics Simulations

Efficient delivery of nanoparticles (NPs) as carriers for biochemical substances is crucial in various biomedical applications. In this study, we systematically investigate the interactions between glycosylated and nonglycosylated forms of Apolipoprotein D (ApoD) with gold nanoparticles (AuNPs) functionalized with different polymer coatings, including polyethylene glycol (PEG) and zwitterionic polymers. Using all-atom molecular dynamics simulations, we demonstrate that glycosylation significantly enhances the adsorption behavior of ApoD on AuNP surfaces, with the extent of this enhancement being dependent on the type (especially the charge property) of the polymer coatings. Notably, while zwitterionic polymers exhibit strong resistance to protein adsorption in their nonglycosylated form, this antifouling capability is diminished when glycosylation is present. Further, our findings reveal that glycosylation not only strengthens the binding energy of proteins but also alters the hydration dynamics at the NP-protein interface. Overall, this study provides a deeper understanding of the role of glycosylation in modulating protein-nanoparticle interactions, which is essential for the design of more effective nanomaterials for precision medicine.