Computer Sumulation Study Of The Interaction Between Protein And Functionalized Titanium Dioxide/Graphene

Graphene and titanium dioxide are two important and commonly used materials in the field of bone reparing.The key to understand their biological effects and their modification potential is to understand the biological/biomaterial interactions on these two surfaces.These knowledges will also serve us as a reference and guide for the development of new biomaterials in the future.Computer simulation is an effective way to study the interaction between biological materials and biomolecules.It can provide us further understanding of the microscopic mechanism in biomaterial/biomolecule interactions,which makes up the shortcomings of experimental research.However,current computational simulation methods still have some drawbacks.For example,quantum mechanical simulation can handle a wide range of elements but are difficult to handle large-scale systems.On the other hand,molecular dynamics simulation can handle systems with large number of atoms but scant force field coverage limits the application in complex material systems.In order to solve this problem,we developed a new set of CHARMM force fields based on first-principles quantum mechanical method.This newly developed force field is suitable for the investigation of complex material surfaces including graphene/functionalized graphene,titanium dioxide/functionalized titanium dioxide and biomolecules.In particular,the effect of surface groups on the biological properties of forgoing materials was investigated.The main research contents are as follows:Graphene as a 2-dimentional material has been widely used in the field of biomedical applications.In this part,molecular dynamics simulations are carried out on the fibrinopeptide-A and graphene surfaces with N and O modifications.A new set of parameters for the CHARMM force field are developed to describe the behaviors of the surfaces.Our results indicate that the existence of most oxygen and nitrogen groups may enhance the interaction between the surfaces and the peptide,whereas the substitutional nitrogen on the graphene surface does not make a big difference.The improvement of interaction is not only because of the functional group on the surface,but also the defective morphology.The defective morphology also clears away the surface water layer.Our results suggest that the interactions between graphene biomolecules can be affected by functionalizing the surface with different types of functional groups,which is in accordance with the theory of material design.Graphene and its derivatives are commonly used as drug delivery devices.The interactions between biomolecule and graphene is critical for further applications.In this part,we investigated the influence of surface functionalization on the adsorption of BMP-2 with graphene surfaces.Four kinds of graphene surface models were built:pristine graphene,reduced graphene oxide,graphene oxide and nitrogen-doped graphene.The results show that the adsorption energy of BMP-2 on graphene oxide is larger than others and the main adsorption site is proline and serine.Besides,BMP-2 will rotate and form a side-material adsorption configuration.The results provided us further understanding of the interaction between BMP-2 and graphene materials,providing theoretical guidance for future material development and design.Titanium dioxide?TiO₂?is a promising biomedical material because it can be modified with various functional groups.However,the mechanism of the interaction between functionalized TiO₂ and biomolecules,especially how the modified TiO₂ regulates subsequent protein functions,still needs further investigation.In this study,we studied the interaction of bone morphogenetic protein-2?BMP-2?with hydroxyl-and phosphite-grafted TiO2 surfaces.A set of force field parameters was developed for hydroxyl and phosphite groups on TiO₂ surfaces,and the adsorption energy between the surface of the functionalized TiO₂ and BMP-2 was calculated.Different coverages of functional groups were applied to the surface to investigate the influence of the functional group density.Grafting phosphite groups on the surface of TiO₂can significantly increase the adsorption energy of the protein and change the orientation of BMP-2 so that the wrist epitope of the BMP-2 molecules is pointing upward.This configuration specifically binds to the BMP receptor type-I on the cell membrane and activates the SMAD1/5/8 signaling pathway for the purpose of enhancing the expression of bone growth and regeneration-related protein.This study shows that it is possible to regulate the function of a protein by deliberately modifying the material surface,which can guide the design of new materials through function-oriented surface modification.