Molecular Dynamics Study Of Biomolecular Adsorption On Biomaterials

Nanomaterials have attracted considerable attention in biological applications ranging from cellular imaging to drug delivery.The surface of nanomaterials have higher free energy than the bulk material itself.Nanomaterials will selectively adsorb biomolecules when they contact with biological fluids,and then biomolecules corona will be formed.Biomolecular corona is considered as the key to realize the nanomaterials function of recognition,targeting,drug loading,sensing and so on.At the same time,it is also the cause of function loss or immune response for some nanomaterials.The composition of the biomolecule corona is not only dependent on the current environment,but also depends on the environments it has gone through.At present,the understanding of biomolecule corona function is far from complete.The formation mechanism is still not clear,while there is still no widely-agreed conclusion on the influences of environment change and material modification on the biomolecules corona yet.The further knowledge of the above questions will make a big difference in the design and application of nanomaterials.To this end,the molecular simulation is used to provide a better understanding of the dynamic mechanism in the microscopic system which is an effective method for the research of the interaction between biological macromolecules and nanomaterials.In this thesis,molecular dynamics simulation method was performed to investigate the biomolecular corona formation on nanomaterials,the interactions between biomolecular and nanomaterials in atomic details,and the effect of ions and material modification on corona-nanomaterial systems.1.Protein could spontaneously form corona on nanomaterial surfaces.Coulombic interaction is the driving force due to the large negatively charged framework.The a cage of zeolite is the adsorption site for key residues due to its small opening and huge volume.Basic amino acids are the key residues in the corona formation process.They share three important features:positively charged ending part has a strong coulombic interaction with nanomaterials;the small diameter of side chains allows the key residues to form a key-lock mode with;the long side chains help the residues to break the obstacle from water layer and react directly with nanomaterial surfaces.By blocking binding site or active site,nanomaterials feedback to the protein activity.2.The influence of solution environment on protein adsorption was studied through the interaction between thrombin and zeolite in water with different counter ions.The counter ion provides a new mechanism for the adsorption of proteins.Acid residues play an important role as well as basic residues.Block effect of water layers on protein adsorption performance is reflected in two aspects:steric hindrance prevents protein getting closer to zeolite;hydrogen bond network formed by polar residues with water layers locks alkaline and acidic residues of protein,meanwhile weakens the interaction of protein with the zeolite.Counter ions in the solution form ion layers with different functions.Monovalent cation layer has no effect on the adsorption of protein.While divalent cation layer in the second water layer provides a strong electrostatic attraction with acidic residues.This attraction enhances the protein adsorption on zeolite surface in case the acidic residues do not cross water layers.The anion layer is also located between the first and the second water layers.A large amount of basic amino acids are adsorbed by anion layer on the competitive with zeolite,which weakens the interaction between the protein and the zeolite.3.By using single wall carbon nanotubes with different surface charge,we studied the influence of the material modification on the biomolecular adsorption process and its conformation changes.Different parts of FAD coenzyme is selectively adsorbed on the different charged carbon nanotubes.Lennard-Jones potential is the driving force in the neutral nanotube system,while the isoalloxazine group of the coenzyme structure is the key part for its adsorption on the outer wall of the carbon nanotubes.Coenzyme structure twisted into U type.Electrostatic attraction is the driving force for positively charged system.CNTs selectively adsorbed the phosphate group of coenzyme structure.While in negatively charged system,the electrostatic repulsion is the main driving force.CNTs formed the weakest adsorption of coenzyme by the rejection of phosphate group.The coenzyme structure closed to the initial crystal conformation.The negative charged system helped to maintain the glucose oxidase activity.