Partial Denaturation of Villin Headpiece upon Binding to a Carbon Nitride Polyaniline (C₃N) Nanosheet

Carbon nitride polyaniline (C₃N) nanosheets, since their recent successful synthesis, have been explored for biomedical applications. However, a thorough study of their interaction with biomolecules is still largely missing. Here, by using all-atom molecular dynamics simulations, we identified the mechanistic determinants of the interaction between a C₃N nanosheet and the prototypical protein villin headpiece (HP35). Our simulations revealed that, upon adsorption, the nanosheet can cause partial denaturation of HP35 by destructing its interior hydrogen bonds plus other native contacts and unwinding its helices. Our study also demonstrated that the C₃N/HP35 interaction energy showed stepwise changes during the binding process and held a strong correlation with the loss of HP35 native contacts. The findings shed light on the detailed molecular mechanism behind the interactions, which might benefit the future applications of C₃N-based nanostructures in biomedicine.