Unravelling biotoxicity of graphdiyne: Molecular dynamics simulation of the interaction between villin headpiece protein and graphdiyne

Abstract Recently, there has been a growing prevalence in the utilization of graphdiyne (GDY) in the field of biomedicine, attributed to its distinctive physical structure and chemical properties. Additionally, its biocompatibility has garnered increasing attention. However, there is a lack of research on the biological effects and physical mechanisms of GDY-protein interactions at the molecular scale. In this study, the villin headpiece subdomain (HP35) served as a representative protein model. Molecular dynamics simulations were employed to investigate the interaction process between the HP35 protein and GDY, as well as the structural evolution of the protein. The data presented in our study demonstrate that GDY can rapidly adsorb HP35 protein and induce denaturation to one of the α -helix structures of HP35 protein. This implies a potential cytotoxicity concern of GDY for biological systems. Compared to graphene, GDY induced less disruption to HP35 protein. This can be attributed to the presence of natural triangular vacancies in GDY, which prevents π – π stacking action and the limited interaction of GDY with HP35 protein is not conducive to the expansion of protein structures. These findings unveil the biological effects of GDY at the molecular level and provide valuable insights for the application of GDY in biomedicine.