Influence of Structured Water Layers on Protein Adsorption Process: A Case Study of Cytochrome c and Carbon Nanotube...

Cytochrome c, an essential protein of the electron transport chain, is known to be capable of amplifying the toxicity of carbon nanomaterials via free-radical generation. To understand their interaction, as well as the more general protein-nanoparticle interaction at molecular levels, we investigate the adsorptions between cytochrome c and carbon nanotubes (CNTs) in dynamic and thermodynamic ways using molecular dynamics simulations. The results reveal a well-defined three-phase process separated by two transition points: the diffusion phase where the protein diffuses in the water box, the lockdown phase I where the protein inserts into the surface-bound water layers and rearranges its conformation to fit to the surface of the CNT, and the lockdown phase II where cytochrome c repels the water molecules standing in its way to the surface of CNT and reaches stable adsorption states. The structured water layers affect the movement of atoms by electrostatic forces. In lockdown phase I, the conformation adjustment of the protein dominates the adsorption process. The most thermally favorable adsorption conformation is determined. It shows that except for the deformation of short β sheets and some portions of α helixes, most of the secondary structures of cytochrome c remain unchanged, implying that most of the functions of cytochrome c are preserved. During these processes, the energy contributions of the hydrophilic residues of cytochrome c are much larger than those of hydrophobic residues. Interestingly, the structured water layers at the CNT surface allow more hydrophilic residues such as Lys to get into close contact with the CNT, which plays a significant role during the anchoring process of adsorption. Our results demonstrate that the heme group is in close contact with the CNT in some of the adsorbed states, which hence provides a way for electron transfer from cytochrome c to the CNT surface.