Study On The Mechanism Of Interfacial Action Between Carbon-based Nanomaterials And Proteins

Carbon-based nanomaterials,such as graphene,graphyne,and carbon nanotubes(CNTs)have demonstrated outstanding mechanical,electrical,thermal and optical properties and hence attracted significant research interest for a wide range of biomedical applications.Due to the wide range of potential biomedical applications brought by these novel graphene family nanomaterials,their interactions with important biological molecules may have potentially adverse effects on the organisthese after these nanoparticles enter the human body,assessment of their toxic potential threats to human health after exposure to these nanoparticles has emerged as an important area in toxicology.Nonetheless,most of the research on graphene toxicology has mainly focused at the cellular and tissue levels.It s only in recent years that state-of-the-art experiments have been carried out to assess graphene's toxicity in vitro and in vivo at the molecular level.Molecular dynamics(MD)simulation has been applied extensively to gain insights into the atomic level mechanism of the interactions between nanomaterials and biomolecules.Here we systematically studied the interfacial interaction mechanisms of four different nanomaterials with proteins using large-scale all-atom MD simulations.Firstly,we focus on how GO can influence the protein-protein interactions(PPI)using the C-terminal DNA-binding domain of human immunodeficiency virus-1(HIV-1)integrase(IN).This domain is known to bind to the viral DNA ends non-specifically in the functional polymerization of the integrase.Here,we investigate how the GO sheet affects the complex of the protein dimer with MD simulations.Detailed analyses of the simulation trajectories reveal that GO could indeed interfere the PPI and potentially disrupt the biological functions of protein complexes in a cell.Secondly,we report an investigation of graphyne binding with CaM.We studied the binding impact of graphyne nanosheet(GYNS)and graphyne quantum dots(GYQD;one-side-surface area of 145 A2)on Ca2+-bound CaM(Holo-CaM)and Ca2+-free CaM(Apo-CaM).Graphyne binding to CaM occurred through strong hydrophobic interactions,indicating possible interference to CaM binding target peptides and hence the Ca2+ signal transduction pathway.On the other hand,the application of nanotechnology to improve disease diagnosis,treatment,monitoring and prevention is the goal of nanomedicine.In this part,we study a functionalized single-walled carbon nanotube(CNT)mimic binding to an HLA-TCR immune complex as a useful attempt of potential nanomedicine for the HIV vaccine development.Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.At last,we compared the influences of hydrophobic 2D-nanomaterials,such as graphene and MoS2 nanosheets,on the first 17 residues of the huntingtin protein(HTT-N17)folding.The comparison helps us further understand the appreciable differences of protein folding on different nanomaterials.Namely,the protein is disordered on the graphene surface but is helical on the MoS2 surface.Despite that the amphiphilic environment at the nanosheet-water interface promotes the folding of the amphipathic proteins(such as HTT-N17),competitions between protein-nanosheet and intra-protein interactions yield very different protein-conformations.Overall,by investigating the interaction between different nanomaterials and proteins,we can go deeper and more systematically to understand the mechanism of interfacial interaction between different nanomaterials and proteins.