A quantitative characterization method for the anti-adhesion effect of a hydrophilic polymer brush coating

Abstract

The present invention discloses a method for quantitatively characterizing the anti-adhesion effect of a hydrophilic polymer brush coating, comprising the following steps: constructing a polymer brush coating model; setting the polymer brush coating model, and the set parameters include the boundary conditions of the calculation system, environmental temperature, selection of potential function, energy minimization, relaxation equilibrium, and output parameters; using the MD method to simulate and calculate the movement and distribution of atoms in the system based on classical Newtonian mechanics, recording the position and velocity information of each atom at each simulation moment until obtaining the atomic trajectory information of long-time simulation; according to the calculated atomic velocity and position information, analyzing and obtaining the thermodynamic parameters of the target system, including the repulsive force of the polymer brush coating against protein adhesion, the interaction between the polymer brush coating and the protein, and the deformation degree of the protein on the surface of the polymer brush coating. It solves the problem that it is difficult to quantitatively characterize the anti-protein adhesion effect on the surface of a hydrophilic polymer brush coating in the existing molecular dynamics simulation technology.

Description

Technical Field

[0001] The present invention relates to the technical field of molecular dynamics simulation, and relates to a method for quantitatively characterizing the anti-adhesion effect of a hydrophilic polymer brush coating, and specifically relates to a method for quantitatively characterizing the anti-adhesion effect of a hydrophilic polymer brush coating based on molecular dynamics simulation. Background Art

[0002] The statements herein only provide background art related to the present invention and do not necessarily constitute prior art.

[0003] Non-specific adhesion occurring on the surface of implantable / interventional medical devices will cause a series of adverse effects, resulting in reduced or even failed device performance. For example, the adhesion and activation of proteins and coagulation factors in blood on the surface of medical devices will trigger the coagulation cascade reaction, leading to the formation of thrombus, and further causing venous blood flow obstruction, thrombophlebitis and embolism, etc. Biosensors for disease diagnosis are seriously interfered with by protein non-specific adhesion in the body fluid environment, such as false positives, reduced signal-to-noise ratio, and damage to specific recognition / reactivity. In addition, ships, underwater vehicles, offshore platforms, etc. are the same as implantable / interventional medical devices and biosensors, facing the problem of protein non-specific adhesion, which has a significant impact on the improvement of their functions and becomes an important factor restricting their application effects.

[0004] At present, a series of methods have been developed to address the problem of surface fouling. Superhydrophobic surfaces with surface micro-nano structures can capture air to form a barrier, significantly reducing the contact area between the surface and the liquid, thereby inhibiting protein adhesion. However, hydraulic pressure, sound pressure, thermal field and surface energy changes pose challenges to the long-term effectiveness of superhydrophobic surfaces, limiting the application of superhydrophobic surfaces. An upgraded strategy is to use micro-nano structures to lock lubricating oil instead of air to form a liquid-infused liquid-repellent surface, and this stable liquid-repellent surface can significantly resist protein adhesion. However, the high preparation difficulty of complex micro / nano structures and the problem of liquid-infused surface failure caused by the loss of intermediate liquid limit its application. There is also a method that does not require surface micro / nano structures, and only needs to graft a polymer brush coating with anti-protein adhesion on the surface, such as hydrophilic polymer brush coatings such as polyethylene glycol, zwitterionic materials and polypeptides.

[0005] Polymer brush coatings have attracted more and more attention due to their important application prospects in the field of anti-fouling surface modification. Solving the problem of surface fouling through polymer brush coatings is considered to have great prospects. Common polymer brush coating materials include hydrophilic polymers such as polyethylene glycol materials, zwitterionic materials, and polypeptides. Generally, it is considered that these hydrophilic polymers can attract water molecules through hydrogen bonds or electrostatic interactions to form a hydration layer. The water molecules in this hydration layer are firmly bound to the surface and can withstand relatively large pressures, so they can serve as a powerful physical and energy barrier against protein adsorption.

[0006] At present, some studies have shown that surface-grafted hydrophilic polymer brush coatings can significantly reduce protein adhesion. However, these studies are basically limited to the field of scientific research, and the polymer brush coatings have not been widely applied in actual engineering. This is mainly because protein adhesion is a complex dynamic process and is affected by factors such as environmental temperature, valence state and ionic strength of salt solutions. At present, experimental methods are still difficult to accurately characterize the interaction relationship between hydrophilic polymer brush coatings and proteins, and to reveal the influence rules of solution molecules such as water molecules and salt ions on protein adhesion.

[0007] The molecular dynamics simulation method (MD) is a computational method based on classical mechanics principles, which can simulate the motion of atoms or molecules in a given potential energy field. This method can provide in-depth understanding of the microscopic structure and dynamic behavior of materials, thus playing an important role in materials science research. In short, as a powerful computational tool, the application of molecular dynamics simulation in materials science research will be more and more extensive, providing stronger support for the development of materials science. Exploring the anti-protein adhesion performance of polymer brush coatings based on molecular dynamics simulation and guiding the development and design of polymer brush coatings have also received extensive attention. In theory, through molecular dynamics simulation, the influence rules of coating materials, structures (grafting density, coating thickness, coating conformation, etc.) on the anti-protein adhesion performance of polymer brush coatings can be quickly explored. Through molecular dynamics simulation, the structure, dynamics and interaction characteristics of the polymer brush coating-water and polymer brush coating-protein interfaces can be deeply understood, and the relationship between the structure of the polymer brush coating and its anti-protein adhesion performance can be understood at the molecular level. However, protein adhesion is a complex process, including the protein breaking through the barrier of the hydration layer on the surface of the hydrophilic polymer and approaching the surface of the polymer brush coating, and the protein undergoes irreversible deformation during the interaction with the polymer brush coating, resulting in protein adhesion. In addition, protein adhesion is also a dynamic process, and the protein on the surface of the hydrophilic polymer brush coating is also affected by the solvation force and has a tendency to detach from the surface of the polymer brush coating. At present, through molecular dynamics simulation, only simple interaction studies such as the binding energy and binding probability between polymer chains and proteins can be realized, and it is difficult to form a quantitative characterization of the anti-protein adhesion of polymer brush coatings based on molecular dynamics simulation. Summary of the Invention

[0008] Aiming at the deficiencies of the existing technology, the purpose of the present invention is to provide a quantitative characterization method for the anti-adhesion effect of hydrophilic polymer brush coatings, covering the ease of protein approaching the polymer brush coating, the mutual influence relationship between the protein and the surface of the polymer brush coating, and the dynamic detachment process of the protein, so as to solve the problem that it is difficult to realize the quantitative characterization of the anti-protein adhesion effect on the surface of hydrophilic polymer brush coatings in the existing molecular dynamics simulation technology, thereby guiding the material selection and structural design of polymer brush coatings and realizing the on-demand preparation of anti-protein adhesion polymer brush coatings.

[0009] To achieve the above object, the present invention is implemented through the following technical solutions:

[0010] A method for quantitatively characterizing the anti-adhesion effect of a hydrophilic polymer brush coating, comprising the following steps: constructing a polymer brush coating model;

[0011] Setting the polymer brush coating model, and the set parameters include the boundary conditions of the calculation system, environmental temperature, selection of potential function, energy minimization, relaxation equilibrium, and output parameters;

[0012] Using the MD method to simulate the motion and distribution of atoms in the system based on classical Newtonian mechanics, recording the position and velocity information of each atom at each simulation moment until the atomic trajectory information of long-time simulation is obtained;

[0013] According to the obtained atomic velocity and position information, analyze and obtain the thermodynamic parameters of the target system, including the repulsive force of the polymer brush coating against protein adhesion, the interaction between the polymer brush coating and the protein, and the deformation degree of the protein on the surface of the polymer brush coating.

[0014] In some embodiments, when constructing the polymer brush coating model, draw the molecular model of the polymer brush coating material through Materials Studio software and perform structure optimization; obtain the CHARMM force field potential energy parameters of the polymer brush coating material (obtained through the CHARMM GUI website (https: / / charmm-gui.org / )), construct the polymer brush coating model through VMD software, and perform solvation treatment.

[0015] Preferably, the substrate of the polymer brush coating model is a silicon substrate, one end of the polymer chain is fixed on the silicon substrate, and the polymer chains are arranged perpendicular to the silicon substrate.

[0016] More preferably, the length of the polymer chain is controllable to simulate the influence of the thickness of the polymer brush coating on the anti-protein adhesion property.

[0017] More preferably, the spacing between the polymer chains is controllable to simulate the influence of the grafting density of the polymer brush coating on the anti-protein adhesion property.

[0018] More preferably, the material of the polymer is selected from polyethylene glycol, phosphorylcholine, carboxybetaine, phosphorylcholine or polypeptides. The material of the polymer is controllable to explore the anti-protein adhesion performance of different brush coating materials.

[0019] More preferably, the solvation treatment is to add ions with different valence states and different concentrations to the solution environment where the polymer brush coating is located.

[0020] More preferably, the ions are chloride ions, sodium ions, calcium ions, magnesium ions or sulfate ions. By subjecting the polymer brush coating to solvation treatment, the effects of solution environments with different valence states and different ionic strengths on the anti-protein adhesion of the polymer brush coating are explored.

[0021] In some embodiments, when setting up the polymer brush coating model, the X, Y, and Z boundaries of the simulation system are all set as periodic boundaries, and the cut-off distance of the short-range Lennard-Jones interaction is set to The time step is 2 fs; energy minimization is performed for 50,000 steps to eliminate bad contacts and reduce the energy of the system; the relaxation time is not less than 2 ns.

[0022] In some embodiments, the environmental temperature is selected according to the application scenario. To explore the effects of different environmental temperatures on the anti-protein adhesion of the polymer brush coating.

[0023] In some embodiments, when using the MD method for simulation calculations, it is divided into three stages, where: in the first stage, the protein is fixed at a set distance from the surface of the polymer brush coating, and then the protein is pulled closer to the surface of the polymer brush coating until the centroid of the protein coincides with the surface of the polymer brush coating, and the position information of the polymer brush coating, the protein, and the solvent is obtained;

[0024] In the second stage, based on the completion of the first stage, the protein is released, and the protein is simulated in an unconstrained state to explore the interaction between the polymer brush coating and the protein;

[0025] In the third stage, based on the completion of the first stage, a pulling force is applied to the protein to make the protein move away from the surface of the polymer brush coating at a set speed until it is sufficiently far away.

[0026] Preferably, the speed of pulling the protein closer to the surface of the polymer brush coating is 0.01 m / s - 0.5 m / s.

[0027] Preferably, the speed of pulling the protein away from the surface of the polymer brush coating is 0.01 m / s - 0.5 m / s.

[0028] Preferably, the "sufficiently far away" means that the distance between the protein and the surface of the polymer brush coating reaches 3 nm.

[0029] Preferably, when extracting and analyzing the simulation data of the first stage, analyze the total repulsive force, the force exerted by the polymer brush coating on the protein, and the force exerted by the solution on the protein during the process of the protein approaching the surface of the polymer brush coating.

[0030] Preferably, when extracting and analyzing the simulation data of the second stage, analyze the force exerted by the polymer brush coating and the force exerted by the solution on the protein on the surface of the polymer brush coating.

[0031] Preferably, when analyzing the simulated data of the third stage, analyze the total repulsive force on the protein during the process of the protein moving away from the protein, the force of the polymeric brush coating on the protein, and the force of the solution on the protein.

[0032] The beneficial effects obtained by one or more of the above embodiments of the present invention are as follows:

[0033] The method for quantitatively characterizing the anti-protein adhesion effect of hydrophilic polymeric brush coatings based on molecular dynamics simulation provided by the present invention can fully simulate the dynamic adhesion process of proteins on the surface of polymeric brush coatings, including the entire process of protein approaching, deforming, and detaching. And the means of evaluating the anti-protein adhesion of the polymeric brush coating is determined by the force on the protein during the dynamic adhesion process. Therefore, the anti-protein adhesion performance of the polymeric brush coating can be quantified and compared, so as to conveniently guide the selection of polymeric brush coating materials and the design of structures, and consider application characteristics such as the solution environment and environmental temperature, and guide the design, preparation, and application of polymeric brush coatings with engineering application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] The specification drawings forming a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention.

[0035] Figure 1 The chemical structural formula of the molecular dynamics model constructed for Example 1 provided by the present invention;

[0036] Figure 2 The molecular dynamics model constructed for Example 1 provided by the present invention;

[0037] Figure 3 Schematic diagram (A) of the protein approaching the surface of the polymeric brush coating in Example 1 provided by the present invention and the force-distance curve (B) when the protein approaches the surface of the polymeric brush coatings of different materials;

[0038] Figure 4 The force source of the protein approaching the surface of the polymeric brush coating in Example 1 provided by the present invention;

[0039] Figure 5 Schematic diagram (A) of the deformation of the protein on the surface of the polymeric brush coating in Example 1 provided by the present invention and the degree of deformation (B) of the protein on the surface of the polymeric brush coatings of different materials;

[0040] Figure 6 Schematic diagram (A) and force condition (B) of the protein on the surface of the polymeric brush coating in Example 1 provided by the present invention;

[0041] Figure 7Schematic diagram (A) of the protein away from the surface of the polymer brush coating in Example 1 provided by the present invention and the force-distance curve (B) when the protein is away from the surface of the polymer brush coating of different materials;

[0042] Figure 8 The source of the force on the protein away from the surface of the polymer brush coating in Example 1 provided by the present invention;

[0043] Figure 9 Force-distance curve of the protein approaching the surface of the polymer brush coating with different grafting densities in Example 2 provided by the present invention;

[0044] Figure 10 The degree of deformation of the protein on the surface of the polymer brush coating with different grafting densities in Example 2 provided by the present invention;

[0045] Figure 11 Force-distance curve of the protein away from the surface of the polymer brush coating with different grafting densities in Example 2 provided by the present invention. Detailed implementation manners

[0046] It should be noted that the following detailed description is illustrative and is intended to provide further illustration of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0047] To better illustrate the purpose, technical solution and advantages of the present invention, the present application will be further described below in conjunction with specific embodiments.

[0048] Example 1

[0049] It should be noted that in this example, the force conditions of the dynamic adhesion process of proteins on the surfaces of polymer brush coatings of different materials are extracted and analyzed to characterize and compare their anti-protein adhesion properties, and to guide the material selection of polymer brush coatings with more excellent anti-protein adhesion properties. Since there are various polymer brush coating materials, but the molecular dynamics modeling and simulation processes of the polymer brush coatings of each material are the same, therefore, in this example, three common polymer brush coating materials are modeled and simulated. This example takes the poly(methacryloyloxyethyl carboxybetaine) polymer brush coating (denoted as PCBMA in the figure), the poly(methacryloyloxyethyl phosphorylcholine) polymer brush coating (denoted as PMPC in the figure), and the poly(methacryloyloxyethyl sulfobetaine) polymer brush coating (denoted as PSBMA in the figure) as examples for explanation. The specific modeling and simulation processes, data extraction and analysis results are as follows:

[0050] The molecular models of poly (methacryloylethyl carboxybetaine) brush coatings, poly (methacryloylethyl phosphorylcholine) brush coatings, and poly (methacryloylethyl sulfobetaine) brush coatings were drawn using Materials Studio software. Each polymer brush chain was polymerized from 15 monomers and its structure was optimized. The chemical structures of the monomers of the polymer brush coatings are as shown in Figure 1 The CHARMM force field potential energy parameters of the three polymer brush coating materials were obtained through the CHARMM GUI website (https: / / charmm-gui.org / ), and the polymer brush coating models were constructed using VMD software. Water molecules were added to the polymer brush models to make the model size a rectangular box, and the polymer brush coating models as shown in Figure 2 were obtained. The distance between polymer chains in the polymer brush coating model was 1.5 nm, and each molecular dynamics model contained 16 polymer brush coating chains in total.

[0051] The simulation parameters were set for the above models respectively. The X, Y, and Z boundaries of the simulation system were all set as periodic boundaries, and the cut-off distance of the short-range Lennard-Jones interaction was set to The time step was 2 fs; the environmental temperature was set to 310 K; energy minimization was performed for 50,000 steps to eliminate bad contacts and reduce the system energy; the relaxation time was 2 ns.

[0052] The above models were simulated and calculated respectively. The MD method is mainly based on classical Newtonian mechanics to simulate the motion and distribution of atoms in the system. That is, the distance between atoms and the potential energy function determine the force between atoms, which in turn leads to the motion and redistribution of atoms. The position and velocity information of each atom at each simulation moment were recorded, and the process was repeated until the atomic trajectory information of long-time simulation was obtained.

[0053] The simulation process was divided into three stages: In the first stage, coagulation factor FXII was selected as the model protein to quantify the anti-protein adhesion strength of the polymer brush coating. The protein was fixed at a position 0.3 nm away from the surface of the polymer brush coating, and then the protein was pulled towards the polymer brush surface at a speed of 0.2 m / s until the center of mass of the protein coincided with the surface of the polymer brush coating.

[0054] The second stage was to obtain the position information of the polymer brush coating, protein, and solvent when the first stage was completed. Then, simulation was carried out in a free simulation state, that is, without adding constraints, to explore the interaction between the polymer brush coating and the protein.

[0055] When the first simulation stage is completed in the third stage, the position information of the aggregated brush coating, protein, and solvent after the first-stage simulation is obtained, and then the protein is pulled away from the surface of the polymeric brush at a speed of 0.2 m / s until the centroid of the protein is sufficiently far away from the polymeric brush coating.

[0056] Data processing: Extract and analyze the simulation data of the first stage in step three. Focus on analyzing the total repulsive force on the protein during the process of the protein approaching the surface of the polymeric brush coating, as well as the force exerted by the polymeric brush coating on the protein and the force exerted by the solution on the protein. By comparing the forces on the protein when approaching the surfaces of polymeric brush coatings made of different materials, it can be found that the repulsive force on the protein is the strongest when approaching the surface of the PSBMA polymeric brush coating, and the weakest when approaching the surface of the PCBMA polymeric brush coating, as Figure 3 shown. This means that the PSBMA polymeric brush coating is more resistant to the approach of the protein, thereby reducing the probability of protein adhesion. Further analyze the source of the force on the protein by decomposing the force on the protein into the force exerted by the polymeric brush coating on the protein and the force exerted by the solution on the protein. It can be found that the source of the repulsive force during the entire approach process is entirely provided by the hydration layer, and in most distances, the hydration repulsive force is greater than the total repulsive force on the protein, and there is a significant attractive force between the polymeric brush coating and the protein, as Figure 4 shown. This is because the hydrophilic polymeric brush coating can attract a high-density layer of water molecules on the surface of the polymeric brush coating through hydration to form a hydration layer. During the approach of the protein, the protein first faces the physical barrier and energy barrier of the hydration layer. For the protein to contact the polymeric brush coating, it must displace the water molecules existing between the protein and the polymeric brush coating. However, the hydration layer between the protein and the polymeric brush coating has a certain stability and is difficult to be squeezed out. Therefore, the solution exerts a repulsive force on the protein. At the same time, the hydration layer avoids the direct contact between the polymeric brush and the protein. According to the L-J potential used in molecular dynamics, two atoms show an attractive force at a relatively long distance, and overall, it shows that the polymeric brush coating and the protein show an attractive state during the entire approach process, that is, the protein is attracted by the polymeric brush coating.

[0057] Data processing: Extract and analyze the simulation data of the second stage in step three. Focus on analyzing the deformation of the protein on the surface of the polymeric brush coating and the force exerted by the polymeric brush coating and the solution on the protein on the surface of the polymeric brush coating. Macroscopically, the protein will avoid contact with the surface of the polymeric brush coating. Therefore, the interaction between the protein and the polymeric brush coating is also crucial. The protein first contacts the surface and then undergoes irreversible deformation and deterioration, thereby adhering to the surface. Therefore, the deformation of the protein on the surface of the polymeric brush coating represents the adhesion strength of the protein on the surface, as Figure 5As shown, proteins will undergo irreversible deformation on the surface of the polymer brush coating. After quantifying the degree of deformation, it was found that the degree of deformation of proteins on the surface of the PSBMA polymer brush coating was the lowest. Further analysis of the forces acting on proteins on the surface of the polymer brush coating revealed that proteins were subjected to the repulsive force of water and the attractive force of the polymer brush coating, as Figure 6 shown.

[0058] Data processing: Extract and analyze the simulation data of the third stage in Step 3. Focus on analyzing the total repulsive force experienced by the protein during the process of moving away from the protein, as well as the force exerted by the polymer brush coating on the protein and the force exerted by the solution on the protein. By comparing the forces acting on the protein when moving away from the surfaces of polymer brush coatings made of different materials, it was found that the protein adhesion force was the weakest when moving away from the surface of the PMPC polymer brush coating, and the strongest when moving away from the surface of the PCBMA polymer brush coating, as Figure 7 shown. This means that the protein is more likely to detach from the surface of the PMPC polymer brush coating, thereby reducing the probability of protein adhesion. Further analysis of the source of the force acting on the protein was carried out, and the force acting on the protein was decomposed into the force exerted by the polymer brush coating on the protein and the force exerted by the solution on the protein. It was found that the solution exerted a repulsive force on the protein throughout the process of moving away. This is because when the protein and the polymer brush coating separate, both will dissolve completely, thereby generating a short-range repulsive force. And the polymer brush coating exerts an attractive force on the protein, as Figure 8 shown.

[0059] Through the simulation in Example 1, it was found that the PSBMA polymer brush coating has stronger anti-protein adhesion ability. Therefore, it can be preferably used as the polymer brush coating material, which has significant guiding significance for the design and preparation of the polymer brush coating.

[0060] Example 2

[0061] It should be noted that in this example, the forces acting on the dynamic adhesion process of proteins on the surfaces of polymer brush coatings with different grafting densities were extracted and analyzed to characterize and compare their anti-protein adhesion properties, and to guide the selection of appropriate polymer brush chain spacings to achieve more excellent anti-protein adhesion performance. Since there are various polymer brush coating materials, but the molecular dynamics modeling and simulation processes of the polymer brush coatings of each material are the same, three common polymer brush coating materials were modeled and simulated in this example. This example takes the poly(methacryloylethyl carboxybetaine) polymer brush coating (denoted as PCBMA in the figure) as an example for explanation. The specific modeling and simulation processes, data extraction, and analysis results are as follows:

[0062] The molecular model of the poly(methacryloylethyl carboxybetaine) polymer brush coating chain was drawn using Materials Studio software. Each polymer brush chain was polymerized from 15 monomers and its structure was optimized. The chemical structure of the polymer brush coating monomers is asFigure 1 As shown. The CHARMM force field potential energy parameters of three polymer brush coating materials were obtained through the CHARMM GUI website (https: / / charmm-gui.org / ), and the polymer brush coating model was constructed using VMD software. Water molecules were added to the polymer brush model to make the model size a rectangular box of. The spacing between polymer chains in the polymer brush coating model is 2 nm, 1.5 nm, and 1.2 nm respectively, forming polymer brush coatings with three grafting densities. In the following introduction, the polymer brush coating models with low, medium, and high grafting densities are represented by low, medium, and high respectively.

[0063] The simulation parameters were set for the above models respectively. The X, Y, and Z boundaries of the simulation system were all set as periodic boundaries, and the cut-off distance of the short-range Lennard-Jones interaction was set to The time step was 2 fs; the environmental temperature was set to 310 K; energy minimization was performed for 50,000 steps to eliminate bad contacts and reduce the system energy; the relaxation time was 2 ns.

[0064] The above models were simulated and calculated respectively. The MD method is mainly based on classical Newtonian mechanics to simulate the motion and distribution of atoms in the system. That is, the distance between atoms and the potential energy function determine the force between atoms, which in turn leads to the motion and redistribution of atoms. The position and velocity information of each atom at each simulation moment were recorded, and the process was repeated until the atomic trajectory information of long-time simulation was obtained.

[0065] The simulation process is divided into three stages: In the first stage, coagulation factor FXII was selected as the model protein to quantify the anti-protein adhesion strength of the polymer brush coating. The protein was fixed at a position 0.3 nm away from the surface of the polymer brush coating, and then the protein was pulled towards the polymer brush surface at a speed of 0.2 m / s until the center of mass of the protein coincided with the surface of the polymer brush coating.

[0066] The second stage is to obtain the position information of the polymer brush coating, protein, and solvent when the first stage is completed. Then, a free simulation state, that is, a state without adding constraints, was used to simulate and explore the interaction between the polymer brush coating and the protein.

[0067] The third stage also occurs when the first simulation stage is completed. The position information of the polymer brush coating, protein, and solvent after the first stage simulation is completed is obtained, and then the protein is pulled away from the polymer brush surface at a speed of 0.2 m / s until the center of mass of the protein is sufficiently far away from the polymer brush coating.

[0068] Data processing and analysis: Extract and analyze the simulated data in the first stage of Step 3. Focus on analyzing the total repulsive force exerted on a protein during its approach to the surface of the polymer brush coating, as well as the forces exerted on the protein by the polymer brush coating and the solution. By comparing the forces acting on the protein when approaching the surfaces of polymer brush coatings with different grafting densities, it can be found that the repulsive force on the protein is the strongest when approaching the surface of the high-grafting-density PCBMA polymer brush coating, and the weakest when approaching the surface of the low-grafting-density PCBMA polymer brush coating, as Figure 9 shown.

[0069] Data processing: Extract and analyze the simulated data in the second stage of Step 3. The protein undergoes irreversible deformation on the surfaces of polymer brush coatings with different grafting densities. After quantifying the degree of deformation, it is found that the degree of deformation of the protein on the surface of the high-grafting-density PCBMA polymer brush coating is the lowest, as Figure 10 shown.

[0070] Data processing: Extract and analyze the simulated data in the third stage of Step 3. By comparing the forces acting on the protein when moving away from the surfaces of PCBMA polymer brush coatings with different grafting densities, it can be found that the protein adhesion force on the protein is the weakest when moving away from the surface of the high-grafting-density PCBMA polymer brush coating, as Figure 11 shown. This means that the protein is more likely to detach from the surface of the high-grafting-density PCBMA polymer brush coating, thereby reducing the probability of protein adhesion.

[0071] Through the simulation in Example 2, it is found that the high-grafting-density PCBMA polymer brush coating has a stronger anti-protein adhesion force, which has significant guiding significance for the design and preparation of polymer brush coatings.

[0072] The above are only the preferred embodiments of the present invention and are not used to limit the present invention. For those skilled in the art, various modifications and changes can be made to the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A quantitative characterization method for the anti-adhesion effect of a hydrophilic polymer brush coating, characterized in that: It includes the following steps: constructing an aggregated brush coating model; setting the aggregated brush coating model, and the set parameters include the boundary conditions of the calculation system, environmental temperature, selection of potential function, energy minimization, relaxation equilibrium, and output parameters; using the MD method to simulate the motion and distribution of atoms in the system based on classical Newtonian mechanics, recording the position and velocity information of each atom at each simulation moment until the atomic trajectory information of long-time simulation is obtained; analyzing and obtaining the thermodynamic parameters of the target system according to the calculated atomic velocity and position information, including the repulsive force of the aggregated brush coating against protein adhesion, the interaction between the aggregated brush coating and the protein, and the deformation degree of the protein on the surface of the aggregated brush coating; when constructing the aggregated brush coating model, draw the molecular model of the aggregated brush coating material through Materials Studio software and perform structure optimization; obtain the CHARMM force field potential energy parameters of the aggregated brush coating material, construct the aggregated brush coating model through VMD software, and perform solvation treatment; the solvation treatment is to add ions with different valence states and different concentrations to the solution environment where the aggregated brush coating is located; the ions are chloride ions, sodium ions, calcium ions, magnesium ions or sulfate ions; When setting up the aggregated brush coating model, the X, Y, and Z boundaries of the simulation system are all set as periodic boundaries, and the cut-off distance of the short-range Lennard-Jones interaction is set to The time step is 2 fs; energy minimization is carried out for 50,000 steps to eliminate bad contacts and reduce the energy of the system; the relaxation time is not less than 2 ns; when using the MD method for simulation calculation, it is divided into three stages, where: in the first stage, the protein is fixed at a set distance from the surface of the aggregated brush coating, and then the protein is pulled closer to the surface of the aggregated brush coating until the center of mass of the protein coincides with the surface of the aggregated brush coating, and the position information of the aggregated brush coating, the protein and the solvent is obtained; the second stage is to release the protein on the basis of the completion of the first stage, and simulate the protein in an unconstrained state to explore the interaction between the aggregated brush coating and the protein; the third stage is to apply a pulling force to the protein on the basis of the completion of the first stage, so that the protein moves away from the surface of the aggregated brush coating at a set speed until it is fully separated.

2. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, wherein: The substrate of the aggregated brush coating model is a silicon substrate, one end of the polymer chain is fixed on the silicon substrate, and the polymer chains are arranged perpendicular to the silicon substrate.

3. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, characterized in that: The length of the polymer chain is controllable to simulate the influence of the thickness of the polymer brush coating on protein adhesion resistance.

4. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, wherein: The spacing between the polymer chains is controllable to simulate the influence of the grafting density of the polymer brush coating on protein adhesion resistance.

5. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, characterized in that: The material of the polymer is selected from polyethylene glycol, phosphorylcholine, carboxybetaine, phosphorylcholine or polypeptides; the material of the polymer is controllable to explore the anti-protein adhesion performance of different brush coating materials.

6. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, characterized in that: The environmental temperature is selected according to the application scenario to explore the influence of different environmental temperatures on the anti-protein adhesion of the aggregated brush coating.

7. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, wherein: The speed of pulling the protein closer to the surface of the aggregated brush coating is 0.01 m / s - 0.5 m / s.

8. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, wherein: The speed of pulling the protein away from the surface of the aggregated brush coating is 0.01 m / s - 0.5 m / s.

9. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, wherein: The "fully separated" means that the distance between the protein and the surface of the aggregated brush coating reaches 3 nm.

10. The quantitative characterization method for the anti-adhesion effect of the hydrophilic polymer brush coating according to claim 1, characterized in that: When extracting and analyzing the simulation data of the first stage, analyze the total repulsive force, the force of the aggregated brush coating on the protein, and the force of the solution on the protein during the process of the protein approaching the surface of the aggregated brush coating; When extracting and analyzing the simulation data of the second stage, analyze the forces exerted on the protein by the polymer brush coating and the solution on the surface of the polymer brush coating; When extracting and analyzing the simulation data of the third stage, analyze the total repulsive force, the force exerted on the protein by the polymer brush coating, and the force exerted on the protein by the solution during the process of the protein moving away from the protein.

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