Structural Consequences of the Villin Headpiece Interaction with a Carbon Nitride Polyaniline (C3N) Nanosheet

ABSTRACT Carbon nitride polyaniline (C 3 N) nanosheets shared a similar structure with graphene and have been utilized in biomedical applications since its recent successful synthesis. However, limited information was known about the interaction of this next-generation nanomaterial with biomolecules, which might hamper its applications in living tissues. Here, by using all-atom molecular dynamics (MD) simulations, we investigated the interaction between a C 3 N nanosheet and the prototypical protein villin headpiece (HP35), in order to identify the mechanistic determinants of such interaction; this knowledge will provide guidelines about C 3 N’s biocompatibility. Our MD simulations revealed that the C 3 N-based nanomaterial caused the partial denaturation of HP35 once the protein was bound on its surface. That is, upon adsorption, we observed the loss of the protein’s interior hydrogen bonds and the native contacts, which were related with unwinding events in the protein’s helices. The protein/C 3 N nanosheet interacting process was dominated by vdW contributions to the energy and the stepwise changes observed in the values of this energy term suggested a gradual unfolding pattern of HP35 during the absorption event. Furthermore, we also found that the interaction energy showed a linear correlation with the native Q ratio of HP35, suggesting that the degree of HP35 unfolding was linearly time-dependent to the interaction energy. Our findings shed light on the underlying molecular mechanism of the potential consequences of C 3 N-based nanostructures to proteins, which might delineate the future applications of these nanomaterials in biomedicine.