The Molecular Modeling And Experimental Studies Of The Influences Of Graphene On The Structure And Fucntion Of Prion

Nowadays,graphene has been applied widely in many fields,including biomedicine field.The potential biomedical applications of graphene mainly include drug/gene delivery,biosensing,bioimaging,antibacterial materials,biocompatible scaffold for cell culture,and so on.Due to the wide applications in the biological field,the biological safety of graphene would not be ignored.It is controversial about how graphene influences the structure and fucntion of protein.In this paper,to explore how the graphene influence the protein conformation,we studied the interaction between graphene and prion protein by computer simulation and experimental methods to observe the conformational changes of prion protein adsorbed on the surface of grapheneand explore the influences of graphene on the structure of prion.In the first part,we introduced briefly the related knowledge of the prion protein and the carbon nano materials with summary.Firstly,we introduced the application of the carbon nanomaterials in the biomedicine field and the toxicity of carbon nanomaterials to human.Secondly,the prion diseases and the pathogenic mechanisms of prion diseases were introduced.Finally,the research progress and related research methods of the interaction between protein and carbon nano materials are summarized.In the first work,we employed atomistic molecular dynamics(MD)simulations to study the effects of graphene on the conformation of prion protein(PrP125-228).Our simulations in explicit solvent suggest that prion protein can be quickly and tightly adsorbed onto graphene,and may reorient when approaching the surface depending on its initial orientation.The most instable parts are the H1 helix and S2-H2 loop,while the other regions are very stable,especially the H2 and H3 helices.It is indirect proof that H1 and S2-H2 loop play the important roles in the process of conformational transition.However,the simulations with implicit solvent showed that the prion protein spread on the graphene surface very fast and lost almost all native structures in all orientations.In general,graphene is able to induce graphene can induce the misfolding of the prion protein.What's more,there may be potential risks in the biological application of graphene.In the second work,to verify further if the graphene can indeed the misfodling of prion,we combined fluorescence quenching and circular dichroism methods to study the influence of graphene on the structure of prion protein.From fluorescence quenching,prion protein can interact with graphene.The changes of the fluorescence intensity indicates that graphene can induce changes in the secondary structure of the prion protein.Circular dichroism analysis indicated that ?-helix content with a significant reduction and ?-sheet content with a slight increase.The obtained results showed that the structure of prion protein was really changed after prion protein is adsorbed on the surface of graphene.The experimental results is consistent with the result of molecular dynamics simulations.In this paper,molecular dynamics simulations,fluorescence quenching method and circular dichroism were applied to study the interaction between prion protein and graphene.What's more,we explore the theoretical mechanism of conformational change of prion from molecular and atomic level.The obtained results has important theoretical value for understanding the biological effects of graphene and other nanomaterials.