Molecular mechanisms governing antibiotic transport in spider silk-riboflavin hydrogels.

Silk hydrogels are emerging as versatile biomaterials for drug delivery owing to their biocompatibility, biodegradability, and tunable hierarchical structure. Their trans-port properties are governed by the interplay between peptide secondary structure, hydration, and intermolecular interactions within the network. Understanding how small drug molecules, penicillin, diffuse through silk-based matrices at the molecular level is therefore critical for rational material design. Here, we studied the molecular mechanisms governing antibiotic, penicillin, transport in a spider silk-riboflavin hydrogel using all-atom molecular dynamics simulations. A 61-residue fragment de-rived from the repetitive domain of major ampullate spidroin 1 (MaSp1) was modeled to represent the silk matrix, and riboflavin was incorporated to examine its influence on supramolecular organization and drug mobility. The riboflavin molecules exhibit markedly restricted mobility, reflecting its propensity to form clusters and engage in strong interactions with the silk peptide matrix. In contrast, penicillin shows comparatively higher diffusivity. Collectively, the results establish a clear structure-dynamics relationship in which supramolecular clustering and peptide-drug interactions regulate antibiotic transport. These findings provide molecular-level insight into how controlled aggregation within silk hydrogels can be strategically leveraged to tune diffusion behavior while preserving matrix integrity.