Mechanism of graphene oxide as an enzyme inhibitor from molecular dynamics simulations

Graphene and its water-soluble derivative, graphene oxide (GO), have attracted huge attention because of their interesting physical and chemical properties, and they have shown wide applications in various fields including biotechnology and biomedicine. Recently, GO has been shown to be the most efficient inhibitor for α-chymotrypsin (ChT) compared with all other artificial inhibitors. However, how GO interacts with bioactive proteins and its potential in enzyme engineering have been rarely explored. In this study, we investigate the interactions between ChT and graphene/GO by using molecular dynamics (MD) simulation. We find that ChT is adsorbed onto the surface of GO or graphene during 100 ns MD simulations. The α-helix of ChT plays as an important anchor to interact with GO. The cationic and hydrophobic residues of ChT form strong interactions with GO, which leads to the deformation of the active site of ChT and the inhibition of ChT. In comparison, the active site of ChT is only slightly affected after ChT adsorbed onto the graphene surface. In addition, the secondary structure of ChT is not affected after it is adsorbed onto GO or graphene surface. Our results illustrate the mechanism of the interaction between GO/graphene and enzyme and provide guidelines for designing efficient artificial inhibitors.