Decoding the Structural Impact of Shape-Engineered Copper Nanoclusters on Lysozyme

The shape and size of copper nanoclusters (CuNCs) play a critical role in governing their interactions with proteins, thereby influencing their potential applications in drug delivery, bioimaging, and therapeutics. In this study, molecular dynamics (MD) simulations were employed to investigate the stability of CuNC-lysozyme complexes in an aqueous environment. Simulations of lysozyme in water using different force fields revealed that its structural stability is strongly force field dependent, with AMBER99SB-ILDN providing the most effective preservation of the secondary structure. To examine the influence of nanocluster geometry on protein-nanocluster binding and stability, CuNCs with different geometries were docked onto lysozyme to form CuNC-lysozyme complexes, which were subsequently subjected to MD simulations. The results demonstrate that the icosahedral CuNC-lysozyme complex exhibits the highest overall stability, with both the protein and the nanocluster retaining their structural conformations throughout the simulations. Overall, these findings highlight the important role of nanocluster geometry in determining the stability of protein-nanomaterial assemblies and provide atomistic-level insights for the rational design of CuNC-based systems for biomedical applications.