A system and method for screening molecules for surface modification of metal electrodes using molecular dynamics simulations

Abstract

This invention provides a system and method for screening surface-modified molecules of metal electrodes using molecular dynamics simulation. The method utilizes Materials Studio 2018, GROMACS 2019.4, and VMD 1.9.3 for modeling, molecular dynamics simulation, and analysis. First, an appropriate model of the electrode-modified molecule under study is constructed. Then, the model is optimized, and control electrodes with no modification and different modifications are set. Next, a solution of the electroactive molecules to be enriched on the working electrode is filled in. Then, molecular dynamics simulation is performed on the system. Finally, the enrichment effect reflected by the trajectory of the electroactive molecules under set conditions, the solvent-accessible surface area, and the interaction energy is compared. This method does not require a large amount of time for actual electrochemical experimental optimization, saves experimental consumables, and provides accurate results. It can be widely applied to the screening of surface-modified molecules of metal electrodes.

Description

Technical Field

[0001] This invention relates to the field of electrochemical sensor technology, and more specifically to a system and method for screening molecules modified on the surface of a metal electrode using molecular dynamics simulation. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Driven by the need to develop homogeneous electrochemical biosensors, higher demands are placed on the ability of detection electrodes to enrich electroactive molecules. Appropriate chemical modification of the electrode surface can effectively improve electrode selectivity and sensitivity. Currently, methods exist for gradually optimizing and screening modified molecules through electrochemical experiments. This method can intuitively and accurately screen out more modified molecules that improve electrode performance; however, the time-consuming nature of electrochemical experiments, the expensive experimental materials, and the degree of randomness in molecule selection significantly limit the efficiency of developing novel electrochemical sensors.

[0004] Molecular dynamics simulations can obtain molecular trajectories of the adsorption process at the electrode-electrolyte solution interface, explore intermolecular interactions, molecular aggregation states, and adsorption driving forces, among other molecular information. Furthermore, molecular dynamics simulations are low-cost, save manpower and resources, are highly reliable, and provide guidance for practical experiments. However, molecular dynamics simulations require sufficient data support. Current work on molecular dynamics simulations mainly focuses on the mechanistic interpretation of existing experiments. This invention utilizes the advantages of molecular dynamics simulations to optimize the design of electrochemical experiments. The experimental results of electrochemical experiments also confirm the reliability of molecular dynamics simulations, significantly improving the efficiency of screening molecules for electrode surface modification. The method of using Materials Studio 2018 for modeling and GROMACS 2019.4 for molecular dynamics simulation screening of molecules for metal electrode surface modification has not been reported domestically or internationally. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a system and method for screening surface-modifying molecules of metal electrodes using molecular dynamics simulations. Specifically, it is a method for screening surface-modifying molecules of metal-based working electrodes for electrochemical sensors using molecular dynamics simulations. The method utilizes Materials Studio 2018, GROMACS 2019.4, and VMD 1.9.3 software to perform molecular dynamics simulations for screening surface-modifying molecules of metal electrodes.

[0006] A first aspect of the present invention provides a method for screening molecules modified on the surface of a metal electrode using molecular dynamics simulations, characterized in that it comprises:

[0007] Prepare and optimize electrode-modified molecular models, and set up contrast electrode models with no modification and different modifications;

[0008] The electrode-modified molecule model or the control electrode model is placed in each simulation box and filled with an electroactive molecule solution to form different electrode-solution systems in each simulation box;

[0009] Energy minimization was performed on different electrode-solution systems, and molecular dynamics simulations were conducted on different electrode-solution systems under isothermal and isochoric conditions to obtain the trajectories of electroactive molecules.

[0010] Based on the trajectory of electroactive molecules, the enrichment effect of different electrode models on electroactive molecules is obtained. Molecular simulation software is used to calculate the solvent-accessible surface area of ​​electroactive molecules to reflect the accumulation state of electroactive molecules on the electrode surface, thereby reflecting the quality of the electrode's enrichment effect on electroactive molecules, and screening out the electrode with the best enrichment effect.

[0011] The electroactive molecule solution is the electroactive molecule solution that the working electrode is expected to enrich.

[0012] Before minimizing the energy of different electrode-solution systems, the atoms on the electrode substrate are fixed.

[0013] The energy minimization method is as follows: the steepest descent method and the conjugate gradient method are used, the maximum interaction between the systems is controlled below 100 kJ / mol, the temperature of each simulation box is kept constant, preferably 310 K; the bond length is constrained, the electrostatic interaction is calculated, and an energy minimization process of 800 steps with a step size of 1 fs is performed.

[0014] The method for preparing and optimizing the electrode-modified molecular model and setting up unmodified and different modified contrast electrode models is as follows: the electrode-modified molecular model and contrast electrode model are constructed using material calculation software, and the electrode-modified molecular model is optimized using the Forcite module and the DMol3 module.

[0015] Place the electrode-modified molecular model or contrast electrode model at the bottom of the simulation box.

[0016] The electroactive molecule solution consists of an appropriate amount of electroactive molecules and water, with the electroactive molecules, as the solute, separated from the electrode by a certain distance.

[0017] A second aspect of the present invention provides a system for screening molecules modified on the surface of a metal electrode using molecular dynamics simulations, comprising:

[0018] Electrode construction module: Prepare and optimize electrode-modified molecular models, and set up contrast electrode models with no modification and different modifications;

[0019] Electrode-solution system construction module: Place the electrode-modified molecule model or the contrast electrode model into each simulation box and fill it with an electroactive molecule solution to form different electrode-solution systems in each simulation box;

[0020] Molecular dynamics simulation module: Minimize energy for different electrode-solution systems, and then perform molecular dynamics simulations under isothermal and isochoric conditions for different electrode-solution systems to obtain the trajectories of electroactive molecules;

[0021] Enrichment effect comparison and optimal electrode screening module: Based on the trajectory of electroactive molecules, the enrichment effect of different electrode models on electroactive molecules is obtained. Molecular simulation software is used to calculate the solvent-accessible surface area of ​​electroactive molecules to reflect the accumulation state of electroactive molecules on the electrode surface, thereby reflecting the quality of the electrode's enrichment effect on electroactive molecules and screening out the electrode with the best enrichment effect.

[0022] A third aspect of the present invention provides a computer device, including a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor executes the program to implement the steps of the above-described molecular dynamics simulation screening method for modifying molecules on the surface of a metal electrode.

[0023] In a fourth aspect, the present invention provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, performs the steps of the above-described molecular dynamics simulation screening method for modifying molecules on the surface of a metal electrode.

[0024] The beneficial effects of this invention are as follows:

[0025] (1) The process of electroactive molecules accumulating on the electrode surface is visually demonstrated at the molecular scale. At the same time as obtaining the screening results, the molecular level interpretation of the screening results can be obtained. This makes the screening process of modifying molecules on the metal electrode surface no longer blind, but traceable and methodical.

[0026] (2) Subsequent electrochemical experiments verified that, while providing accurate results, the method described in this invention significantly reduced costs, greatly shortened the experimental cycle, and improved the efficiency of screening molecules modified on the surface of metal electrodes. The method described in this invention has significant advantages over traditional electrochemical methods for screening molecules modified on the surface of electrodes. Attached Figure Description

[0027] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0028] Figures 1(a) and 1(b) show the optimization of the coverage of mercaptobenzoic acid (MBA) and mercaptopropionic acid (MPA) on the surface of nanoporous gold (NPG) in Example 1 of the present invention.

[0029] Figures 2(a), 2(b), and 2(c) are snapshots of the adsorption of 1MB on NPG, MPA / NPG, and MBA / NPG in Example 1 of the present invention, respectively.

[0030] Figure 3 The change in solvent accessible surface area (SASA) during the adsorption process of 1MB on NPG, MPA / NPG, and MBA / NPG surfaces in Example 1 of this invention is shown.

[0031] Figure 4 This is a comparison of the interaction energies of MBA / NPG and MPA / NPG on MB adsorption in Example 1 of the present invention.

[0032] Figure 5 This is a comparison of the total interaction energies of MBA / NPG and MPA / NPG on MB adsorption in Example 1 of the present invention.

[0033] Figure 6 and Figure 7 This is an electrochemical verification of Example 1 of the present invention. Detailed Implementation

[0034] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0035] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0036] In some typical embodiments of the present invention, a method for screening molecules modified on the surface of a metal electrode using molecular dynamics simulation is provided, characterized by comprising:

[0037] Prepare and optimize electrode-modified molecular models, and set up contrast electrode models with no modification and different modifications;

[0038] The electrode-modified molecule model or the control electrode model is placed in each simulation box and filled with an electroactive molecule solution to form different electrode-solution systems in each simulation box;

[0039] Energy minimization was performed on different electrode-solution systems, and molecular dynamics simulations were conducted on different electrode-solution systems under isothermal and isochoric conditions to obtain the trajectories of electroactive molecules.

[0040] Based on the trajectory of electroactive molecules, the enrichment effect of different electrode models on electroactive molecules is obtained. Molecular simulation software is used to calculate the solvent-accessible surface area of ​​electroactive molecules to reflect the accumulation state of electroactive molecules on the electrode surface, thereby reflecting the quality of the electrode's enrichment effect on electroactive molecules, and screening out the electrode with the best enrichment effect.

[0041] First, judge by the molecular trajectory. If the molecular trajectory does not show obvious differences, then use the interaction energy to judge. The solvent surface area is used to verify the conclusions made by the interaction energy and molecular trajectory.

[0042] In some embodiments of this implementation, the electroactive molecule solution is an electroactive molecule solution that the working electrode is expected to enrich.

[0043] In some embodiments of this implementation, the electrode substrate atoms are immobilized before energy minimization is performed on different electrode-solution systems.

[0044] In some embodiments of this implementation, the energy minimization method is as follows: using the steepest descent method and the conjugate gradient method, the maximum interaction between the systems is controlled below 100 kJ / mol, the temperature of each simulation box is kept constant, preferably 310 K; the bond length is constrained, the electrostatic interaction is calculated, and an energy minimization process of 800 steps with a step size of 1 fs is performed.

[0045] In some embodiments of this implementation, the method for preparing and optimizing the electrode-modified molecular model and setting up unmodified and different modified contrast electrode models is as follows: the electrode-modified molecular model and the contrast electrode model are constructed using material calculation software, and the electrode-modified molecular model is optimized using the Forcite module and the DMol3 module.

[0046] The Forcite and DMol3 modules are optimization calculation tools in the Materials Studio software. After building the model using the modeling tools in Materials Studio, the parameters are set in the Forcite and DMol3 modules before calculation.

[0047] In some embodiments of this implementation, the electrode-modified molecule model or contrast electrode model is placed at the bottom of the simulation box.

[0048] In some embodiments of this implementation, the electroactive molecule solution is an appropriate amount of electroactive molecules and water, with the electroactive molecules, as solutes, separated from the electrodes by a certain distance.

[0049] In another typical embodiment of the present invention, a system for screening molecules modified on the surface of a metal electrode using molecular dynamics simulation is provided, comprising:

[0050] Electrode construction module: Prepare and optimize electrode-modified molecular models, and set up contrast electrode models with no modification and different modifications;

[0051] Electrode-solution system construction module: Place the electrode-modified molecule model or the contrast electrode model into each simulation box and fill it with an electroactive molecule solution to form different electrode-solution systems in each simulation box;

[0052] Molecular dynamics simulation module: Minimize energy for different electrode-solution systems, and then perform molecular dynamics simulations under isothermal and isochoric conditions for different electrode-solution systems to obtain the trajectories of electroactive molecules;

[0053] Enrichment effect comparison and optimal electrode screening module: Based on the trajectory of electroactive molecules, the enrichment effect of different electrode models on electroactive molecules is obtained. Molecular simulation software is used to calculate the solvent-accessible surface area of ​​electroactive molecules to reflect the accumulation state of electroactive molecules on the electrode surface, thereby reflecting the quality of the electrode's enrichment effect on electroactive molecules and screening out the electrode with the best enrichment effect.

[0054] In another typical embodiment of the present invention, a computer device is provided, including a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that the processor executes the program to implement the steps of the above-described molecular dynamics simulation screening method for modifying molecules on the surface of metal electrodes.

[0055] In another typical embodiment of the present invention, a computer-readable storage medium is provided, on which a computer program is stored, which, when executed by a processor, performs the steps of the above-described method for screening molecules modified on the surface of a metal electrode using molecular dynamics simulation.

[0056] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0057] Example 1

[0058] Screening of surface-modifying molecules to enhance the enrichment of methylene blue (MB) by nanoporous gold (NPG) electrodes. The methods of this invention were used to study the enhancing effects of surface-modifying molecules that enhance MB enrichment, such as mercaptobenzoic acid (MBA) and mercaptopropionic acid (MPA).

[0059] (1) The crystal structure of gold was derived from Materials Studio 2018. Based on the structural characteristics of NPG, the gold (2 0 0) plane was cut as the NPG electrode surface, and the NPG electrode was constructed.

[0060] (2) The structures of MBA and MPA were optimized using the DMol3 module, and the two electrode systems of MBA / NPG and MPA / NPG were optimized using the Forcite module to obtain the most stable state of the two electrode systems, and the MBA / NPG and MPA / NPG electrodes were constructed accordingly.

[0061] (3) Export the molecular model and topology file of MB from the Automated Topology Builder (ATB) website, obtain the topology file of Au from the literature, and obtain the topology files of MBA / NPG and MPA / NPG using the x2top command of GROMACS 2019.4 software. The suffix of the topology file is .top. Change the suffix to .itp to obtain MB+.itp, Cl-.itp, Au.itp, Au-MBA.itp, and Au-MPA.itp;

[0062] (4) Use GROMACS 2019.4 software to construct a simulation box. Place the optimized electrodes in (1) and (2) into the bottom of the simulation box, fill it with 25 MB+ and 25 Cl-, and then fill it with water so that the 25 MB+ and 25 Cl- are separated from the electrode surface by about 2 nm, so as to see more clearly the process of electroactive molecules enriching to the electrode surface. Use the .itp file obtained in (2) to write the topology file of the whole box. The file extension is .top, and the files are NPG.top, NPG-MBA.top, and NPG-MPA.top are obtained.

[0063] (5) Create an index file with the suffix .ndx, group all molecules of the electrode substrate into one group and name it freeze. Add freezegrps=freeze and freezedim=Y YY to the minimum.mdp and nvt.mdp files to make the atoms of the electrode substrate fixed during subsequent energy minimization and molecular dynamics simulation under isothermal-isochoric ensemble.

[0064] (6) The steepest descent method and the conjugate gradient method are used to minimize the energy of each system. The maximum interaction between the systems is controlled below 100 kJ / mol. The temperature of each simulation box is kept constant by the V-rescale isothermal coupling algorithm. The Lincs algorithm is used to constrain all bond lengths. The particle mesh Ewald (PME) summation method is used to calculate electrostatic interactions. The joint atomic force field GROMOS54a7 force field is used to perform an 800-step energy minimization process with a step size of 1 fs. The generated files are named npgem, mbaem, and mpaem respectively.

[0065] (7) Using the npgem.gro, mbaem.gro and mpaem.gro files as the initial state, and with the same calculation conditions as in (6), run a molecular dynamics simulation for 50 ns under isothermal-isochoric ensemble (NVT). The generated files are named npgnvt, mbanvt and mpanvt to obtain the motion trajectories of each molecule in the box.

[0066] (8) The optimization of the coverage of the modified molecules performed by Materials Studio 2018 provides guidance for the optimization of the modification concentration of MBA and MPA on the NPG electrode surface. According to the optimization results of Materials Studio 2018, the optimal coverage of MBA is about 33% and that of MPA is about 50%. This is consistent with the trend of the results of subsequent electrochemical verification. The optimal concentration of MPA modified solution is slightly higher than that of MBA.

[0067] (9) The motion trajectory of electroactive molecules was analyzed using VMD 1.9.3 visualization software. npgnvt.gro, mbanvt.gro and mpanvt.gro were opened in VMD 1.9.3 respectively, and the trajectory files npgnvt.xtc, mbanvt.xtc and mpanvt.xtc were imported respectively. The effect of different electrode models on the enrichment of electroactive molecules was observed. The results showed that MBA / NPG had a slightly better enrichment effect on MB than MPA / NPG, and both were much better than NPG.

[0068] (10) The solvent accessible surface area (SASA) of electroactive molecules was calculated using GROMACS 2019.4 to reflect the accumulation state of electroactive molecules on the electrode surface. It was found that the adsorption process of MB by MBA / NPG was carried out in the form of monomolecular adsorption. The adsorption of MB by MPA / NPG was mainly aggregate adsorption in the early stage. After reaching the electrode surface, MB gradually dispersed into monomolecular adsorption and then reached equilibrium. After reaching equilibrium, the adsorption of MB by NPG was both monomolecular adsorption and aggregate adsorption.

[0069] (11) The interaction energies of NPG, MBA / NPG, and MPA / NPG with MB were calculated using GROMACS 2019.4. The interaction energy of NPG with MB is much smaller than that of MBA / NPG and MPA / NPG, so it will not be discussed further. The interaction energy of MB with MBA / NPG and MPA / NPG was compared. The results also predicted that MBA had the best modification effect. Furthermore, the interaction energy diagram showed that the electrostatic attraction of MBA / NPG and MPA / NPG to MB was very close. The reason why MBA / NPG has a better enrichment effect on MB than MPA / NPG is that MBA / NPG has a stronger van der Waals force on MB.

[0070] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method of screening a molecule for modifying a surface of a metal electrode by molecular dynamics simulation, characterized by, The method comprises the following steps: Preparation and optimization of electrode-modified molecule model, setting of unmodified and different modified comparative electrode models; The electrode-modified molecule model or the comparative electrode model is placed in each simulation box, and an electroactive molecule solution is filled in each simulation box to form different electrode-solution systems in each simulation box; Energy minimization is performed on the different electrode-solution systems, and then molecular dynamics simulation under isothermal and isochoric conditions is performed on the different electrode-solution systems to obtain the motion trajectory of the electroactive molecule; The enrichment effect of different electrode models on the electroactive molecule is obtained according to the motion trajectory of the electroactive molecule, and the solvent accessible surface area of the electroactive molecule is calculated by using a molecular simulation software to reflect the accumulation state of the electroactive molecule on the electrode surface, thereby reflecting the enrichment effect of the electrode on the electroactive molecule, and the electrode with the best enrichment effect is screened out.

2. A method of screening a molecule for modifying a surface of a metal electrode by molecular dynamics simulation according to claim 1, wherein The electroactive molecule solution is a solution of an electroactive molecule that is expected to be enriched by a working electrode.

3. The method of screening a molecule for modifying a surface of a metal electrode by a molecular dynamics simulation according to claim 1, wherein Before the energy minimization is performed on the different electrode-solution systems, the electrode substrate atoms are fixed.

4. The method of screening a molecule for modifying a surface of a metal electrode by a molecular dynamics simulation according to claim 1, wherein The energy minimization method is as follows: the steepest descent method and the conjugate gradient method are used, the maximum interaction between systems is controlled to be below 100 kJ / mol, the temperature of each simulation box is kept constant, the bond length is constrained, the electrostatic interaction is calculated, and an energy minimization process with a step of 1 fs and 800 steps is performed.

5. A method of screening for a molecule to modify the surface of a metal electrode by molecular dynamics simulation according to claim 4, wherein The temperature of each simulation box is 310 K.

6. The method of screening a molecule for modifying a surface of a metal electrode by molecular dynamics simulation according to claim 1, wherein The method for preparing and optimizing the electrode-modified molecule model and setting the unmodified and different modified comparative electrode models is as follows: a material calculation software is used to construct the electrode-modified molecule model and the comparative electrode model, and the Forcite module and the DMol3 module are used to optimize the electrode-modified molecule model.

7. The method of screening a molecule for modifying a surface of a metal electrode by a molecular dynamics simulation according to claim 1, wherein The electrode-modified molecule model or the comparative electrode model is placed at the bottom of the simulation box.

8. The method of screening a molecule for modifying a surface of a metal electrode by a molecular dynamics simulation according to claim 1, wherein The electroactive molecule solution is a proper amount of electroactive molecule and water, and the electroactive molecule as a solute is separated from the electrode by a certain distance.

9. A system for screening a metal electrode surface modifying molecule by molecular dynamics simulation, characterized by, The method comprises the following steps: An electrode construction module: preparation and optimization of electrode-modified molecule model, setting of unmodified and different modified comparative electrode models; An electrode-solution system construction module: the electrode-modified molecule model or the comparative electrode model is placed in each simulation box, and an electroactive molecule solution is filled in each simulation box to form different electrode-solution systems in each simulation box; A molecular dynamics simulation module: energy minimization is performed on the different electrode-solution systems, and then molecular dynamics simulation under isothermal and isochoric conditions is performed on the different electrode-solution systems to obtain the motion trajectory of the electroactive molecule; An enrichment effect comparison and best electrode screening module: the enrichment effect of different electrode models on the electroactive molecule is obtained according to the motion trajectory of the electroactive molecule, and the solvent accessible surface area of the electroactive molecule is calculated by using a molecular simulation software to reflect the accumulation state of the electroactive molecule on the electrode surface, thereby reflecting the enrichment effect of the electrode on the electroactive molecule, and the electrode with the best enrichment effect is screened out.

10. A computer device comprising a memory, a processor, and a computer program stored on the memory and executable on the processor, characterized in that, The processor executes the program to implement the steps of the method in any one of claims 1-8.

11. A computer readable storage medium, characterized in that, The computer program is stored on the storage medium and is executed by the processor to implement the steps of the method in any one of claims 1-8.

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