| In recent years,as a quasi zero dimensional nanomaterial,graphene quantum dots(GQDs)have strong quantum confinement effect and edge effect and exhibit characteristics including excellent photoelectric properties,low cytotoxicity and high biocompatibility and biodegradability.GQDs which combined the advantages of graphene and quantum dots have been widely used in biomedicine fields,such as bioimaging,biosensor,drug carrier and so on.It has been illustrated that GQDs could be used for anti-cancer drugs and genes delivering into cells.However,the research of GQDs is still in the initial stage so far,the role of GQDs in drug delivery,the interacting mechanisms with doxorubicin and the cytotoxicity of GQDs remain unclear,which restrict their practical applications.Molecular dynamics(MD)simulation has been applied extensively to gain insights into the atomic level mechanism of the interactions between nanomaterials and biomolecules.In this thesis,we systematically studied the role of GQDs in drug delivery,the adsorption of doxorubicin on GQDs and the impact of GQDs on protein structure using all-atom MD simulations.Besides,we investigate the interaction between calcite(104)surface and SCA-1 to understand the mechanism of inorganic material and biology molecules.The research work and corresponding results were summarized as follows:1.The structure,thermodynamics and dynamic properties of model drugs,doxorubicin and deoxyadenosine,translocation into a POPC lipid membrane with the assistance of GQDs were investigated via the MD simulation and free energy calculation.The simulation results imply that GQD19 can facilitate the permeation of model drugs into the lipid membrane on the nanosecond timescale with less deformation of the cell membrane structure.More importantly,free energy calculations further revealed that the translocation free energy of doxorubicin or deoxyadenosine permeating into the lipid bilayer could be significantly reduced with the assistance of GQD19.Our results suggest that GQDs with appropriate size may assist in the drug delivery process by reducing the translocation free energy permeating into the biomembrane.2.The adsorption behaviour of doxorubicin on graphene oxide quantum dots with different sizes,oxidation degrees and residues composition were studied.The results showed that the larger size and lower oxidation degree lead to stronger interaction.Specifically,the increase of carboxyl groups at the edge of graphene oxide quantum dots is beneficial to enhance the interaction,while the effect of hydroxyl groups in central has two sides.3.The changes in the structure of protein villin headpiece(HP35)when adsorbed on graphene oxide quantum dots(GOQD)with different sizes and oxidation degrees were investigated.The results showed that HP35 not only formed strong ?-? stacking with GOQD surface through aromatic residues but also interacted with other residues through oxygen-containing groups.HP35 has a stronger interaction with GOQDs with larger size and smaller oxidation degree.GOQD had little effect on the structure of HP35 protein in 500 ns simulation,and no cytotoxicity was observed.4.The adsorption behaviour of SCA-1 protein on the calcite(104)surface with several different starting orientations in an explicit water environment was systematically investigated.The results indicate that the positively charged and polar residues are the dominant residues for protein adsorption on the calcite(104)surface,and the strong electrostatic interaction drives the binding of the model protein to the surface.The hydrogen bond bridge was found to play an important role in surface interactions as well.These results also demonstrate that SCA-1 is relatively rigid.The results of the orientation calculation suggest that the dipole moment of the protein tends to remain parallel to calcite in most stable cases,which was confirmed by electrostatic potential isosurfaces analysis. |
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