Spectroscopic and computational insights into protein interactions on silver-decorated covalent organic frameworks...

Despite rapid progress in COF-based biomaterials, no study has yet explored the molecular-level interaction mechanism of a protein with a metal-COF hybrid. This study provides a detailed understanding of the interaction between lysozyme and Ag@COF by integrating experimental biophysical analyses with molecular docking and DFT calculations. In this work, a silver nanoparticle-embedded covalent organic framework (Ag@COF) was prepared using a simple post-synthetic method. Structural and spectroscopic studies confirmed the framework structure, while electron microscopy showed an even distribution of silver particles within the porous framework. Interactions with lysozyme were investigated using spectroscopic methods, which indicated stable binding and only minor structural changes in the protein. Molecular docking supported these findings by identifying favorable interaction sites, with a binding energy of -214.0. Density functional theory (DFT) calculations revealed stabilizing non-covalent forces between Ag and the COF backbone. Dynamic light scattering confirmed concentration-dependent complex formation, while antibacterial tests against Escherichia coli and Enterococcus faecalis showed concentration-dependent inhibition, with a minimum inhibitory concentration (MIC) of 64 μg/mL against E. coli and 128 μg/mL against E. faecalis, supported by microscopy evidence of membrane damage, supported by microscopy evidence of membrane damage. This combined computational and experimental approach provides the first clear understanding of how proteins interact with Ag@COF surfaces, thereby guiding the future design of bioactive COF hybrid materials. Further biological studies are required to validate the broader biomedical applicability of Ag@COF.