Mechanism of hydroxylation-regulated protein corona on graphdiyne via coarse-grained potential.

We derive coarse-grained interaction potentials for graphdiyne-protein systems by first constructing all-atom force fields, thereby enabling large-scale simulations of protein corona formation on graphdiyne nanomaterials. Using these potentials, we elucidate the molecular mechanism by which surface hydroxylation tunes protein corona composition in human blood plasma. We identify tryptophan, tyrosine, and proline as the amino acid residues most sensitive to hydroxylation, unravel how hydroxylation modulates corona composition among drug-delivery-relevant functional proteins, and pinpoint the optimal degree of hydroxylation for tuning the biological identity of graphdiyne. The developed coarse-grained potentials and the uncovered molecular mechanisms provide valuable theoretical guidance for the rational design of graphdiyne-based nanomaterials in biomedical applications.