A method for visualizing the hydration layer on the surface of a hydrophilic polymer brush coating and quantitatively analyzing its properties

Abstract

The present invention discloses a method for visualizing the hydration layer on the surface of a hydrophilic polymer brush coating and quantitatively analyzing its properties, comprising the following steps: constructing a polymer brush coating model and performing a solvation treatment; setting parameters for the polymer brush coating model; using a molecular dynamics method to record the position and velocity information of each atom at each simulation moment, and obtaining the atomic trajectory information of a long-term simulation; analyzing and obtaining the thermodynamic parameters of the object system based on the obtained atomic velocity and position information, and analyzing the volume, density, and hydrogen bond network information of the hydration layer formed on the surface of the polymer brush coating. The method solves the problem that it is difficult to realize the visualization research of the hydration layer on the surface of the hydrophilic polymer brush coating and the quantitative research of the properties such as the volume, density, hydrogen bond network, and water molecule distribution of the hydration layer in the existing molecular dynamics simulation technology.

Description

Technical Field

[0001] The invention relates to the technical field of molecular dynamics simulation, and in particular to a method for visualizing a hydration layer on the surface of a hydrophilic polymer brush coating and quantitatively analyzing its properties. Background Art

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

[0003] The hull, implanted / interventional medical devices, biosensors, etc. face fouling problems, which have a significant impact on the improvement of their functions and become an important bottleneck restricting the development of technology. For example, the non-specific adsorption of proteins on the surface of biomedical implants can cause foreign body reactions in the human body, which is a major challenge and difficulty that needs to be overcome in biomedical research and clinical practice. The coagulation reaction on the surface of medical devices in contact with blood can lead to the formation of thrombi, which in turn causes venous blood flow obstruction, thrombophlebitis and embolism; implant materials that act as drug carriers and tissue scaffolds can trigger human immune recognition, leading to tissue deformation, pain and infection; and the surface of the ship will also form an environmental film due to the adhesion of pollutants such as proteins in the ocean on the surface, which will lead to the formation of biofilms, and then cause biological fouling, resulting in high navigation resistance, high fuel consumption, high greenhouse gas emissions and high navigation costs.

[0004] Polymer brush coatings have attracted more and more attention due to their important application prospects in the field of anti-fouling surface modification. It is believed that polymer brush coatings have great prospects for solving surface fouling problems. Common polymer brush coating materials include hydrophilic polymers such as polyethylene glycol materials, zwitterionic materials and peptides. It is generally believed that these hydrophilic polymers can attract water molecules through hydrogen bonds or electrostatic interactions to form a hydration layer. The water molecules in the hydration layer are firmly bound to the surface and can withstand greater pressure, thus serving as a strong physical and energy barrier against protein adsorption.

[0005] It is precisely because of the hydration properties of polymer brush coatings that they have the potential for antifouling modification. At present, the existence of a hydration layer on the surface of polymer brush coatings can be determined by experimental methods. However, the specific information of the hydration layer on the surface of polymer brush coatings, such as density, water molecule orientation, hydrogen bond distribution and other properties, cannot be determined by microscopic experimental observation methods such as nuclear magnetic resonance spectroscopy, X-ray diffraction, infrared spectroscopy and atomic force microscopy.

[0006] The prospect of characterizing polymer materials and exploring their hydration properties through molecular dynamics simulation has also received widespread attention. However, the exploration methods and characterization means of the hydration properties of polymers as a whole are quite different from those of single polymer chains, and there is currently no relevant information on the visualization of the hydration layer of hydrophilic polymer brush coatings and revealing the volume, density, hydrogen bond network, water molecule distribution and other information of the hydration layer. Summary of the invention

[0007] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a method for visualizing the hydration layer on the surface of a hydrophilic polymer brush coating and quantitatively analyzing its properties, so as to solve the problem that it is difficult to realize the visualization study of the hydration layer on the surface of a hydrophilic polymer brush coating and the quantitative study of the properties such as the volume, density, hydrogen bond network, and water molecule distribution of the hydration layer in the existing molecular dynamics simulation technology.

[0008] In order to achieve the above object, the present invention is implemented through the following technical solutions:

[0009] A method for visualizing a hydration layer on a surface of a hydrophilic polymer brush coating and quantitatively analyzing its properties comprises the following steps:

[0010] Construct a polymer brush coating model and perform solvation treatment;

[0011] Set parameters for the polymer brush coating model;

[0012] The molecular dynamics method is used to record the position and velocity information of each atom at each simulation moment, and obtain the atomic trajectory information of long-term simulation;

[0013] According to the atomic velocity and position information obtained, the thermodynamic parameters of the object system are analyzed, and the volume, density, and hydrogen bond network information of the hydration layer formed on the surface of the polymer brush coating are analyzed.

[0014] In some embodiments, when constructing a polymer brush coating model, Materials Studio software is used to draw a molecular model of the polymer brush coating material and perform structural optimization; the CHARMM force field potential energy parameters of the polymer brush coating material are obtained, and the polymer brush coating model is constructed using VMD software.

[0015] Preferably, the polymer brush coating model is that a section of the polymer chain is fixed on the silicon substrate, and the polymer chain is arranged perpendicular to the silicon substrate.

[0016] Further preferably, the length of the polymer chain can be controlled to simulate the effect of the thickness of the polymer brush coating on the hydration properties.

[0017] Further preferably, the distance between polymer chains is controllable to simulate the effect of grafting density of polymer brush coating on hydration performance.

[0018] Further preferably, the material of the polymer brush coating is polyethylene glycol, phosphorylcholine, carboxybetaine, phosphorylcholine or polypeptide, so as to explore the hydration properties of different polymer brush coating materials.

[0019] In some embodiments, the ions added during the solvation treatment are chloride ions, sodium ions, calcium ions, magnesium ions, or sulfate ions, in order to explore the effects of solution environments with different valence states and different ionic strengths on the hydration properties of the polymer brushes.

[0020] In some embodiments, the parameters of the polymer brush coating model are set, specifically: the three boundaries of the simulation system X, Y, and Z are all set to periodic boundaries, and the cutoff distance of the short-range Lennard-Jones interaction is set to The time step was 2 fs; energy minimization was performed for 50,000 steps to eliminate poor contacts and reduce system energy; and the relaxation time was not less than 2 ns.

[0021] In some embodiments, the simulation process for obtaining atomic trajectory information for a long time simulation is divided into two stages. In the first stage, the polymer chain is set as a flexible chain, and the force condition is calculated in the potential energy function of the CHARMM force field, and the velocity and acceleration parameters are calculated based on this, and then the chain relaxation is performed to obtain a fully developed polymer brush coating structure;

[0022] The second stage is to obtain the position information of the polymer brush coating chain when the first stage is completed, ignore its velocity and acceleration information, and set it as a rigid body. The polymer chain maintains this position in subsequent simulations and no longer moves or deforms. Only the trajectory distribution and hydrogen bond network of water molecules are recorded.

[0023] Preferably, the simulation time of the first stage is not less than 10 ns, and the simulation time of the second stage is not less than 10 ns.

[0024] Preferably, when analyzing and acquiring the thermodynamic parameters of the object system based on the acquired atomic velocity and position information, the simulation data of the second stage is extracted and analyzed.

[0025] Further preferably, the polymer brush coating model is divided into The average density of water molecules and polymer brush coating in the unit in the second stage is calculated to realize the visualization study of the hydration layer on the surface of polymer brush coating.

[0026] More preferably, the volume and density of the hydration layer on the surface of the polymer brush coating are extracted and analyzed to evaluate the hydration performance of the polymer brush coating.

[0027] More preferably, the average number of hydrogen bonds formed by each water molecule is counted along the Z-axis direction to characterize the hydrogen bond network on the surface of the polymer brush coating.

[0028] The beneficial effects achieved by one or more embodiments of the present invention are as follows:

[0029] The visualization of the polymer brush coating surface hydration layer and the quantitative characterization method of its properties provided by the present invention can make the polymer brush coating surface hydration layer visible and characterizable. By characterizing the volume, density and stability parameters of the polymer surface hydration layer such as hydrogen bond network strength, the hydration properties of different polymer brush coating materials can be compared and studied to optimize the polymer brush coating materials. In addition, the thickness and grafting density of the polymer brush coating can be controlled to optimize the polymer brush coating structure to achieve stronger hydration performance. The parameters such as the ionic strength and ionic valence of the salt solution and the ambient temperature can also be adjusted to explore the influence of the salt solution and the ambient temperature on the hydration properties of the polymer brush coating, and determine the applicability of the polymer brush coating in different environments. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0031] Figure 1 The chemical structural formula and polymer chain model of the molecular dynamics model constructed in Example 1 and Example 2 provided by the present invention;

[0032] Figure 2 The molecular dynamics model constructed according to Example 1 provided by the present invention;

[0033] Figure 3 A visualization diagram of the surface hydration layer of the polymer brush coating of Example 1 provided by the present invention;

[0034] Figure 4 Schematic diagram of a high-density hydration layer on the surface of a polymer brush coating of different materials provided in Example 1 of the present invention;

[0035] Figure 5 The volume of the high-density hydrated layer on the surface of the polymer brush coating of different materials provided in Example 1 of the present invention;

[0036] Figure 6 The hydrogen bonding network at the polymer brush coating-water interface of different materials provided in Example 1 of the present invention;

[0037] Figure 7 A schematic diagram of a high-density hydration layer on the surface of a polymer brush coating with different grafting densities according to Example 2 of the present invention;

[0038] Figure 8 The volume of the high-density hydrated layer on the surface of the polymer brush coating with different grafting densities provided in Example 2 of the present invention;

[0039] Fig. 9 The hydrogen bond network at the polymer brush coating-water interface with different grafting densities provided in Example 2 of the present invention. DETAILED DESCRIPTION

[0040] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0041] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present application will be further described below in conjunction with specific embodiments.

[0042] Example 1

[0043] It is worth noting that this embodiment extracts and analyzes parameters such as the volume and density of the surface hydration layer of polymer brush coatings of different materials, the distribution of hydrogen bond networks, etc., to compare the hydration properties of polymer brush coatings of different materials. Since polymer brush coating materials are diverse, but the molecular dynamics modeling and simulation processes are consistent, this embodiment models and simulates three common polymer brush coating materials. This embodiment uses methacryloylethyl carboxybetaine polymer brush coating (represented by PCBMA in the figure), methacryloylethyl phosphorylcholine polymer brush coating (represented by PMPC in the figure), and methacryloylethyl sulfonobetaine polymer brush coating (represented by PSBMA in the figure) as examples for explanation. The specific modeling and simulation process, data extraction and analysis results are as follows:

[0044] The molecular models of methacryloylethyl carboxybetaine polymer brush coating chains, methacryloylethyl phosphorylcholine polymer brush coating chains, and methacryloylethyl sulfobetaine polymer brush coating chains were drawn using Materials Studio software. Each polymer brush coating chain is polymerized from 15 monomers and the structure is optimized. The chemical structure of the polymer brush coating monomer and the molecular model of the polymer chain are shown in Figure 1. Figure 1 shown.

[0045] 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 model was constructed using VMD software. Water molecules were added to the polymer brush model to change the model size to The rectangular box of the polymer brush coating model is obtained as Figure 2In the polymer brush coating model, the distance between polymer chains is 1.5 nm, and each molecular dynamics model contains 16 polymer chains.

[0046] The simulation parameters of the above models were set respectively. The three boundaries of the simulation system X, Y, and Z were set as periodic boundaries, and the cutoff distance of the short-range Lennard-Jones interaction was set as The time step was 2 fs; energy minimization was performed for 50,000 steps to eliminate poor contacts and reduce system energy; the relaxation time was 2 ns.

[0047] The above models were simulated and calculated respectively. The MD method is mainly based on classical Newtonian mechanics to simulate the movement and distribution of atoms in the calculation system. That is, the distance between atoms and the potential energy function determine the force between atoms, which in turn leads to the movement and redistribution of atoms. The position and velocity information of each atom at each simulation moment is recorded, and the cycle is repeated until the atomic trajectory information with a simulation time of not less than 10ns is obtained.

[0048] The simulation process is divided into two stages. In the first stage, the polymer chain is set as a flexible chain, and the force is calculated in the potential energy function of the CHARMM force field, and the velocity and acceleration parameters are calculated based on this, and further chain relaxation is performed to obtain a fully developed polymer brush coating structure. The simulation time of the first stage is not less than 10ns. The second stage is to obtain the position information of the polymer brush coating chain after completing the first stage, ignore the velocity and acceleration information, and set it as a rigid body. The polymer brush coating chain will remain in this position in the subsequent simulation, and will no longer move or deform. Only the trajectory distribution and hydrogen bond network of water molecules will be considered later. The simulation time of the second stage is 15ns.

[0049] Data analysis, based on the atomic velocity and position information obtained through calculation, analyzes the thermodynamic parameters of the object system, etc., focusing on analyzing the volume, density, hydrogen bond network and other information of the hydration layer formed on the surface of the polymer brush coating.

[0050] In order to realize the visualization study of the hydration layer on the surface of the polymer brush coating, the polymer brush coating model is divided into The average density of water molecules and polymer brush coating in each unit is calculated in the following way: in the simulation time range of 15ns, the density of water molecules in each unit is calculated every 0.001ns. During the whole simulation process, each unit will obtain 15,000 water molecule density data, and the average of these 15,000 water molecule densities is taken as the average water molecule density of each unit in the second simulation stage. The statistical method of the average density of polymer brush is the same as that of the average density of water molecules. Figure 3As shown in the figure, the blue unit represents the location of the polymer brush coating, and the red unit represents the area where the high-density water molecules are located. Statistics show that there is a layer of high-density water molecule units on the surface of the polymer brush coating, and the density of water molecules is nearly 2g / cm 3 , almost twice as much as body water, such as Figure 4 This is the high-density hydration layer on the surface of the polymer brush coating.

[0051] The volume of the hydration layer on the surface of the polymer brush coating was further extracted and analyzed. Figure 5 As shown, the volume of the hydration layer on the surface of methacryloylethylcarboxybetaine polymer brush coating (PCBMA) is the largest, indicating that it has the strongest hydration performance.

[0052] Then, the average number of hydrogen bonds formed by each water molecule along the Z-axis was counted to characterize the hydrogen bond network on the surface of the polymer brush coating. Figure 6 As shown in the figure, an enhanced hydrogen bond network appears at the interface between methacryloylethyl carboxybetaine polymer brush coating (PCBMA) and methacryloylethyl sulfobetaine polymer brush coating (PSBMA) and water, which makes the association between the polymer brush coating and the hydration layer more firm. However, there is no significantly enhanced hydrogen bond network at the interface between methacryloylethyl phosphorylcholine polymer brush coating (PMPC) and water, indicating that its hydration layer is less stable.

[0053] Example 2

[0054] It is worth noting that this example extracts and analyzes the volume and density of the surface hydration layer of polymer brush coatings with different grafting densities, the distribution of hydrogen bond networks and other parameters to compare the hydration performance of polymer brush coatings with different grafting densities. Therefore, this example takes methacryloylethyl carboxybetaine polymer brush coating (represented by PCBMA in the figure) as an example for explanation. The specific modeling and simulation process, data extraction and analysis results are as follows:

[0055] The methacryloylethyl carboxybetaine polymer brush coating chain was drawn by Materials Studio software. Each polymer brush coating chain is composed of 15 monomers and the structure is optimized. The chemical structure of the methacryloylethyl carboxybetaine polymer brush coating monomer and the molecular model of the polymer chain are shown in Figure 1. 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 model was constructed through VMD software. Water molecules were added to the polymer brush model to change the model size to The rectangular box of the polymer brush coating model is obtained as Figure 2As shown. The distances between polymer chains in the polymer brush coating model are 2nm, 1.5nm, and 1.2nm, respectively, forming polymer brush coatings with three grafting densities. The model size is controlled to be 8nm, so the polymer brush coating models with different grafting densities contain 9, 16, and 25 polymer brush coating chains, respectively. The polymer brush coating models with three grafting densities are represented by low, medium, and high, respectively.

[0056] The simulation parameters of the above models were set respectively. The three boundaries of the simulation system X, Y, and Z were set as periodic boundaries, and the cutoff distance of the short-range Lennard-Jones interaction was set as The time step was 2 fs. Energy minimization was performed for 50,000 steps to eliminate bad contacts and reduce the system energy, with a relaxation time of 2 ns.

[0057] The above models were simulated and calculated respectively. The MD method is mainly based on classical Newtonian mechanics to simulate the movement and distribution of atoms in the calculation system. That is, the distance between atoms and the potential energy function determine the force between atoms, which in turn leads to the movement and redistribution of atoms. The position and velocity information of each atom at each simulation moment is recorded, and the cycle is repeated until the atomic trajectory information of long-term simulation under certain conditions is obtained.

[0058] The simulation process is divided into two stages. In the first stage, the polymer chain is set as a flexible chain, and the force is calculated in the potential energy function of the CHARMM force field, and the velocity acceleration parameters are calculated based on this, and further chain relaxation is performed to obtain a fully developed polymer brush coating structure. The simulation time of the first stage is not less than 10ns. The second stage is to obtain the position information of the polymer brush coating chain when the first stage is completed, and the velocity and acceleration information are omitted, and it is set as a rigid body. The polymer brush coating chain will remain in this position in the subsequent simulation, and will no longer move or deform. Only the trajectory distribution of water molecules and the hydrogen bond network will be considered in the subsequent simulation.

[0059] Data analysis, based on the atomic velocity and position information obtained through calculation, analyzes the thermodynamic parameters of the object system, etc., focusing on analyzing the volume, density, hydrogen bond network and other information of the hydration layer formed on the surface of the polymer brush coating.

[0060] In order to realize the visualization study of the hydration layer on the surface of the polymer brush coating, the polymer brush coating model is divided into The average density of water molecules and polymer brush coating in the unit in the second simulation stage is calculated. Figure 7 As shown in the figure, the blue unit represents the location of the polymer brush coating, and the red unit represents the area where the high-density water molecules are located. Statistics show that there is a layer of high-density water molecule units on the surface of the polymer brush coating of each grafting density, so a high-density hydration layer can be formed.

[0061] The volume of the hydration layer on the surface of the polymer brush coating was further extracted and analyzed. Figure 8 The surface hydration layer volume of the methacryloylethylcarboxybetaine polymer brush coating (PCBMA) with a medium grafting density is the highest, indicating that it has the strongest hydration performance.

[0062] Then, the average number of hydrogen bonds formed by each water molecule along the Z-axis was counted to characterize the hydrogen bond network on the surface of the polymer brush coating. Fig. 9 As shown, with the increase of the grafting density of methacryloylethylcarboxybetaine polymer brush coating (PCBMA), the hydrogen bond network at the polymer brush coating-water interface is enhanced, which indicates that the stability of its hydration layer is enhanced, that is, the increase of the grafting density is beneficial to the stability of the hydration layer.

[0063] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties, characterized in that: The steps include: Construct a polymer brush coating model and perform solvation treatment; Set parameters for the polymer brush coating model; The molecular dynamics method is used to record the position and velocity information of each atom at each simulation moment, and obtain the atomic trajectory information of long-term simulation; According to the atomic velocity and position information obtained, the thermodynamic parameters of the object system are analyzed, and the volume, density, and hydrogen bond network information of the hydration layer formed on the surface of the polymer brush coating are analyzed; When constructing the polymer brush coating model, Materials Studio software was used to draw the molecular model of the polymer brush coating material and perform structural optimization; the CHARMM force field potential energy parameters of the polymer brush coating material were obtained, and the polymer brush coating model was constructed using VMD software; The simulation process for obtaining atomic trajectory information for long-term simulation is divided into two stages. In the first stage, the polymer chain is set as a flexible chain, and the force is calculated in the potential energy function of the CHARMM force field, and the velocity and acceleration parameters are calculated based on this. Then, the chain is relaxed to obtain the fully developed polymer brush coating structure. The second stage is to obtain the position information of the polymer brush coating chain when the first stage is completed, ignore its velocity and acceleration information, and set it as a rigid body. The polymer chain maintains this position in the subsequent simulation and no longer moves or deforms. Only the trajectory distribution and hydrogen bond network of water molecules are recorded; The simulation time of the first stage is not less than 10ns.

2. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 1, characterized in that: The polymer brush coating model is that one section of the polymer chain is fixed on the silicon substrate, and the polymer chain is arranged perpendicular to the silicon substrate.

3. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 2, characterized in that: The length of the polymer chains can be controlled to simulate the effect of polymer brush coating thickness on hydration properties.

4. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 2, characterized in that: The spacing between polymer chains can be controlled to simulate the effect of grafting density of polymer brush coatings on hydration properties.

5. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 2, characterized in that: The material of the polymer brush coating is polyethylene glycol, phosphorylcholine, carboxybetaine, phosphorylcholine or polypeptide.

6. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 1, characterized in that: The ions added during the solvation treatment are chloride ions, sodium ions, calcium ions, magnesium ions or sulfate ions.

7. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 1, characterized in that: The parameters of the polymer brush coating model are set as follows: the three boundaries of the simulation system X, Y, and Z are set as periodic boundaries, and the cutoff distance of the short-range Lennard-Jones interaction is set as The time step was 2 fs; energy minimization was performed for 50,000 steps to eliminate poor contacts and reduce system energy; and the relaxation time was not less than 2 ns.

8. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 1, characterized in that: Based on the acquired atomic velocity and position information, the second stage simulation data is extracted and analyzed when analyzing the thermodynamic parameters of the object system.

9. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 8, characterized in that: The polymer brush coating model is divided into The average density of water molecules and polymer brush coating in the unit in the second stage is calculated to realize the visualization study of the hydration layer on the surface of polymer brush coating.

10. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 9, characterized in that: The volume and density of the hydrated layer on the surface of the polymer brush coating were extracted and analyzed.

11. The method for visualizing the surface hydration layer of a hydrophilic polymer brush coating and quantitatively analyzing its properties according to claim 10, characterized in that: The average number of hydrogen bonds formed by each water molecule was counted along the Z-axis to characterize the hydrogen bond network on the surface of the polymer brush coating.

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