Method for regulating and controlling conductivity of drug DNA compound based on de-coherence model

Abstract

The invention relates to a method for regulating and controlling the conductivity of a drug-DNA compound based on a de-coherence model, and belongs to the field of electrochemistry. The invention aims to solve the technical problems of difficult separation of solvent and counter-ion coupling effect, poor experiment control repeatability and drug-DNA compound conductivity regulation and control in the prior art. The method comprises the following steps: constructing a DNA molecular model by using an NAB software package, adding counter ions by using an energy minimization mode, and respectively calculating electrical properties such as conductivity and transmission rate of the DNA molecular model in a water environment and a vacuum environment through a density functional theory and a non-equilibrium Green function formula; then, the same electrical property calculation is carried out on the drug-DNA compound embedded with the drug small molecules, and the conductivity of the drug-DNA compound is regulated and controlled by changing the solvent environment and the number of counter ions. Through molecular dynamics calculation, the synergistic effect of the Na ion concentration and the environment dielectric constant on charge transfer is disclosed, and the conductivity regulation and control range is widened; a de-coherence model is adopted to correct the thermal fluctuation influence, and the calculation precision is improved compared with a traditional method; a quantitative evaluation system for combination of MAR70 / Cyan drug molecules and DNA is established, and a new way is provided for development of molecular sensors.

Description

Technical Field

[0001] The present invention belongs to the field of electrochemistry and relates to a method for regulating the conductivity of a drug-DNA complex based on a decoherence model Background Art

[0002] DNA has become one of the main materials in molecular electronics due to its self-assembly characteristics and long-range charge transport characteristics. It naturally exists in a solvent environment surrounded by water and salt molecules. The conductivity of DNA depends on environmental factors such as the dielectric constant of the solvent, the position, or the local density of the DNA counterions surrounding it. In previous studies, it has been demonstrated that the solvent environment affects the DNA conformation. In order to reveal only the role of the solvent, in this model study, we keep the DNA structure fixed and only change the dielectric constant of the environment

[0003] In addition to the solvent, counterions also exist near the sugar-phosphate backbone. Positively charged counterions (such as Na+) are attracted to the negative charges on the backbone phosphate groups. Previous studies have considered the influence of counterions and concluded that they also affect DNA conductance. However, due to excessive techniques and approximations, it is difficult to draw clear conclusions. The rich diversity of the conclusions depends on the experimental and modeling methods and requires continuous systematic research on this issue. In this model study, we focus on investigating the role of Na+ ions and the intrinsic conductance determined by the solvent environment through DNA

[0004] It is difficult to separate the coupling effect between the solvent and the counterions, and it is difficult for existing methods to study the influence of a certain factor alone, such as only changing the dielectric constant while ignoring the ion concentration. It is experimentally difficult to precisely control the DNA structure and the spatial distribution of counterions, resulting in poor data repeatability. Early models did not consider the decoherence effect (such as thermal fluctuations and environmental noise), resulting in a large deviation between the calculated conductivity result and the experimental value. There are few studies on drug-DNA complexes and few examples of systematic analysis. Traditional methods (such as electrochemical measurements) can only obtain macroscopic conductivity data and cannot analyze the charge transport mechanism at the molecular level. The adjustment of the number of counterions relies on empirical experiments (such as solution concentration adjustment) and lacks theoretical prediction support

[0005] DNA small molecules are widely used in gene therapy fields such as anti-cancer and anti-tumor, so the interaction between small molecules and DNA has attracted the attention of many scientists. Through the study of the electrical properties of DNA, it is found that there is a certain relationship between drug concentration or drug binding efficiency and DNA conductivity, and the process of drug-DNA interaction can be transformed into the change of DNA conductivity. More importantly, this discovery provides a new idea for the controllable modulation of DNA electrical properties, which is crucial for the realization of DNA-based nanoelectronic devices. In addition to the research value in disease treatment, some recent experiments have begun to study the influence of drug molecule binding on DNA conductivity. Summary of the Invention

[0006] In view of this, the present invention uses NAB and Amber software to construct an energy-minimized DNA / drug complex structure, combines density functional theory (DFT) with non-equilibrium Green's function (NEGF), and realizes the calculation of conductivity at the molecular level. By fixing the DNA structure and only adjusting the solvent (water / vacuum) and Na + quantity (such as deleting from 10 to 9), the calculation of the conductivity of the two is clarified. The purpose of the present invention is to provide a method for regulating the conductivity of drug-DNA complexes based on the decoherence model.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] The present invention provides a method for regulating the conductivity of drug-DNA complexes based on the decoherence model, including the following steps:

[0009] (a) Construct a target DNA molecule or drug-DNA complex model, and the base sequence of the DNA molecule is CGATCG;

[0010] (b) Add a water box to the molecule or complex system constructed in step (a), and make the system electrically neutral by adjusting the number of Na + ions;

[0011] (c) Place the system of step (b) in a water environment or a vacuum environment, and delete at least one Na + ion to change the charge state of the system;

[0012] (d) Use density functional theory combined with the decoherent non-equilibrium Green's function method to calculate the conductivity under different charge states or environments;

[0013] (e) According to the conductivity calculation results of step (d), regulate the conductivity by adjusting the number of Na + ions or the solvent environment;

[0014] Preferably, the method for constructing the DNA molecular model in step (a) is specifically as follows:

[0015] Use the NAB software to input the CGATCG sequence to generate the initial structure file of B-DNA; import the initial structure file into the molecular dynamics software, load the atomic force field and the hydraulic field, and save the topology file and the trajectory file; perform energy minimization on the system to stabilize the structure;

[0016] Preferably, the drug is the MAR70 or Cyan drug molecule;

[0017] Preferably, in step (a), obtain the crystal structure of the complex containing MAR70 or Cyan from the PDB database, delete the surrounding water molecules and optimize the structure; load the drug and the DNA molecular force field in the molecular dynamics software to generate the complex topology file and the trajectory file; perform energy minimization on the system to stabilize the structure;

[0018] Preferably, in step (b), the number of added Na + ions is 10, and the stability of the system is maintained through energy minimization;

[0019] Preferably, the charge state is electrically neutral or positively charged.

[0020] Preferably, in step (b), perform DFT calculations using the B3LYP functional and the 6-31G(d,p) basis set to obtain the system Hamiltonian matrix; correct the Hamiltonian matrix based on the decoherence model and simulate the solvent effect by combining the polarizable continuum model; calculate the conductivity and the transmission rate through the non-equilibrium Green's function method.

[0021] Preferably, the regulation method of the naked B-DNA molecule is as follows:

[0022] In an aqueous environment, deleting one Na + can increase the conductivity of the naked B-DNA from 1.30×10 -6 G0 to 2.82×10 - 6 G0;

[0023] In a vacuum, deleting one Na + can increase the conductivity of the naked B-DNA from 1.27×10 -8 G0 to 2.95×10 -6 G0.

[0024] Preferably, the conductivity regulation range of the drug-DNA complex is:

[0025] In the MAR70-DNA complex in an aqueous environment, after deleting one Na + ion, the conductivity changes from 4.51×10-7 G0 changes to 1.19×10 -6 G0;

[0026] In a vacuum environment, one Na is removed + After that, the conductivity changes from 4.07×10 -5 G0 to 4.69×10 -5 G0;

[0027] In an aqueous environment of the Cyan-DNA complex, one Na is removed + After that, the conductivity increases from 1.27×10 -6 G0 to 2.09×10 -6 G0;

[0028] In a vacuum environment, after removing one Na+ from a neutral molecule, the conductivity changes from 9.82×10 -7 G0 to 1.88×10 -6 G0;

[0029] Preferably, the method is used for evaluating the binding efficiency of drug molecules to DNA.

[0030] The beneficial effects of the present invention are as follows:

[0031] The present invention discloses a method for regulating the conductivity of drug-DNA complexes. The drug-DNA complexes are MAR70-DNA complex and Cyan-DNA complex respectively. The present invention minimizes the energy of the complexes through AMBER molecular dynamics software to achieve a stable structural state. This method can change the conductivity of drug-DNA complexes only by changing the number of Na+ and the solvent environment for calculation, without relying on other experiments. At the same time, this method also has good portability, and different drug molecules have different effects on changing the conductivity. This method studies for the first time the change in the conductivity of drug-DNA complexes. The method is simple and convenient, providing a new possibility for the fabrication of DNA molecular sensors.

[0032] Other advantages, objects and features of the present invention will be set forth to some extent in the following description, and to some extent, will be obvious to those skilled in the art based on the study of the following text, or can be taught from the practice of the present invention. The objects and other advantages of the present invention can be realized and obtained through the following description. Description of the Drawings

[0033] In order to make the objects, technical solutions and advantages of the present invention clearer, the present invention will be described in detail preferably with reference to the accompanying drawings, wherein:

[0034] Figure 1Among them, a, b, and c are respectively the crystal structures of the complexes of naked B-DNA, MAR70-DNA, and Cyan-DNA;

[0035] Figure 2 Among them, a and b are the effects of Na+ on the conductivity and transport rate of naked B-DNA in an aqueous environment;

[0036] Figure 3 Among them, a and b are the effects of Na+ on the conductivity and transport rate of naked B-DNA in a vacuum environment;

[0037] Figure 4 Among them, a and b are respectively the two-dimensional DOS diagrams of B-DNA in an aqueous environment and a dry environment;

[0038] Figure 5 Among them, a and b are respectively the effects of Na+ on the conductivity and transport rate of MAR70-DNA in an aqueous environment;

[0039] Figure 6 Among them, a and b are respectively the effects of Na+ on the conductivity and transport rate of MAR70-DNA in a vacuum environment;

[0040] Figure 7 Among them, a and b are respectively the two-dimensional DOS diagrams of MAR70-DNA in an aqueous environment and a dry environment;

[0041] Figure 8 Among them, a and b are respectively the effects of Na+ on the conductivity and transport rate of Cyan-DNA in an aqueous environment;

[0042] Figure 9 Among them, a and b are respectively the effects of Na+ on the conductivity and transport rate of Cyan-DNA in a vacuum environment;

[0043] Figure 10 Among them, a and b are respectively the two-dimensional DOS diagrams of Cyan-DNA in an aqueous environment and a dry environment. Specific embodiments

[0044] The following specific examples illustrate the implementation manners of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific implementation manners. Various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the diagrams provided in the following examples only illustrate the basic concept of the present invention in a schematic manner. Without conflict, the following examples and the features in the examples can be combined with each other.

[0045] Among them, the attached drawings are only for illustrative purposes, showing only schematic diagrams rather than actual object diagrams, and should not be construed as limiting the present invention; in order to better illustrate the embodiments of the present invention, some components in the attached drawings will be omitted, enlarged or reduced, which do not represent the dimensions of the actual product; for those skilled in the art, it is understandable that some well-known structures and their descriptions in the attached drawings may be omitted.

[0046] In the attached drawings of the embodiments of the present invention, the same or similar reference numerals correspond to the same or similar components; in the description of the present invention, it should be understood that if there are terms such as "upper", "lower", "left", "right", "front", "rear", etc. indicating the orientation or positional relationship, they are based on the orientation or positional relationship shown in the attached drawings. This is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, the terms describing the positional relationship in the attached drawings are only for illustrative purposes and should not be construed as limiting the present invention. For those of ordinary skill in the art, the specific meanings of the above terms can be understood according to specific circumstances.

[0047] Embodiment 1

[0048] First, calculate the electrical properties of naked B-DNA after changing the solvent environment and Na+ ions in an energy-minimized manner. The specific steps are as follows:

[0049] (1) First, use the NAB software package to construct B-type DNA with the base sequence C-G-A-T-C-G, and then use the Amber software to perform energy minimization on it. First, upload the PDB file of the DNA to the server, use the tleap tool to load the atomic force field and the force field of water, save its top (topology) file and crd (trajectory) file, then add Na+ ions to make the whole system electrically neutral, then create an octahedral water box around the DNA, and save its top file and crd file again. Finally, perform energy minimization, and thus a stable structure with counterions is obtained.

[0050] (2) Perform DFT calculations on the obtained structure using GaussianView. In order to only reveal the role of the solvent, in this model study, we keep the DNA structure fixed and only change the dielectric constant of the environment in our calculations to simulate the situations in vacuum and water environments.

[0051] (3) In this calculation, the electrical properties of three molecules were calculated, namely B-DNA with the base sequence CGATCG, the MAR70-DNA complex with the base sequence CGATCG, and the Cyan-DNA complex.

[0052] (4) This simulation is divided into four cases. The first case is the electrical properties of a molecule with 10 Na+ ions added in an aqueous environment; the second case is the electrical properties of a molecule with 10 Na+ ions added in a vacuum environment; the third case is the electrical properties of a molecule with one randomly deleted Na+ ion based on 10 Na+ ions in an aqueous environment; the fourth case is the electrical properties of a molecule with one randomly deleted Na+ ion based on 10 Na+ ions in a vacuum environment.

[0053] (5) The calculation process of electrical properties is as follows: First, run the Gaussian input file to obtain the output log file and chk file, where the log file contains the energy level information of the molecule. Then obtain H0 and S0, obtain the Fock matrix and Overlap matrix, and then use python and matlab scripts to execute the non-equilibrium Green's function method to calculate the electrical properties such as the conductivity and transmission rate of the molecule.

[0054] Example 2

[0055] (1) Model construction: By the method of Example 1, a B-DNA with the base sequence CGATCG was constructed using the NAB software package, and energy minimization was performed using Amber. Na+ ions were added to make the system electrically neutral, and a stable structure was obtained (as shown, where a is the structure of naked DNA and b is the crystal structure of MAR70-DNA), and hydrogen was added through GaussianView5.0, and the structure after hydrogen addition was uploaded to the server. Figure 1 shown, where a is the structure of naked DNA and b is the crystal structure of MAR70-DNA), and the structure after hydrogen addition was uploaded to the server.

[0056] (2) DFT calculation: In this paper, the discrete Fourier transform and non-equilibrium Green's function were adopted, and the decoherence effect was considered. The B3LYP functional and the 6-31G(d, p) Gaussian 09 basis set were used to study DFT. Here, we implicitly calculated the solvent effect using the polarizable continuum model. Subsequently, they were transformed into an orthogonal Hamiltonian matrix using the Löwdin transformation to obtain the corresponding results. On this basis, the decoherence method of non-equilibrium Green's function was used to calculate several important electrical signals in naked DNA.

[0057] (3) Calculating parameters related to electrical signals: Observing the influence of Na+ ions on electrical properties in an aqueous environment, first is the change in the energy band. When DNA is electrically neutral, the HOMO energy level of DNA is -5.32 eV, the LUMO energy level is -1.14 eV, and the bandgap is 4.18 eV; while after randomly deleting one Na+ ion from DNA, the HOMO energy level and LUMO energy level are -5.29 eV and -1.12 eV respectively, and the bandgap is 4.17 eV, with almost no change; and the conductivity of the electrically neutral molecule is 1.30×10 -6G0, the conductivity changes by 2.82×10 -6 G0, showing a 17% increase. The change in the transmission rate of the two also shows the same trend, as Figure 2 shown.

[0058] (4) Observe the change in the electrical properties of Na+ ions in a vacuum environment: When DNA is electrically neutral, the HOMO energy level of DNA is -3.24 eV, the LUMO energy level is -2.34 eV, and the bandgap is 0.9 eV; after randomly deleting a Na+ ion from DNA, the HOMO and LUMO energy levels are -2.75 eV and -2.44 eV respectively, and the bandgap is 0.31 eV; it is worth mentioning that in the case of being electrically neutral, the HOMO energy levels in a vacuum environment and an aqueous environment are -3.24 eV and -5.32 eV respectively, which shows the influence of the solvent environment on the DNA energy levels. The electrical conductivity of the electrically neutral molecule is 1.27×10 -8 G0, the conductivity changes by 2.95×10 -6 G0, showing a 231% increase. The change in the transmission rate of the two also shows the same trend.

[0059] Example 3

[0060] (1) Model construction: Download the crystal structure of the MAR70-DNA complex (PDB ID: 1R68) from the RCSB website, then use GaussianView5.0 to delete the surrounding water molecules, and use Amber for energy minimization. Add Na+ ions to make the system electrically neutral, obtain a stable structure, and hydrogenate it through GaussianView5.0, and upload the hydrogenated structure to the server.

[0061] (2) DFT calculation: This paper uses the discrete Fourier transform and non-equilibrium Green's function, and considers the decoherence effect. Apply the B3LYP functional and the 6-31G(d, p) Gaussian 09 basis set to study DFT. Here, we implicitly calculate the solvent effect using the polarizable continuum model. Subsequently, use the Löwdin transformation to convert them into an orthogonal Hamiltonian matrix to obtain the corresponding results. On this basis, use the decoherence method of non-equilibrium Green's function to calculate several important electrical signals in bare DNA.

[0062] (3) Calculate relevant parameters of the electrical signal: Observe the influence of Na+ ions on the electrical properties of the crystal complex in an aqueous environment. First is the change in the energy band. When DNA is electrically neutral, the HOMO energy level of DNA is -5.07 eV, the LUMO energy level is -2.98 eV, and the bandgap is 2.09 eV; after randomly deleting one Na+ ion from DNA, the HOMO energy level and the LUMO energy level are -5.05 eV and -2.97 eV respectively, and the bandgap is 2.08 eV, with almost no change; while the electrical conductivity of the electrically neutral molecule is 4.51×10 -7 G0, and the change in electrical conductivity after deleting one Na+ is 1.19×10 -6 G0, an increase of 163%.

[0063] (4) Observe the change of Na+ ions on the electrical properties in a vacuum environment: When the complex crystal is electrically neutral, the HOMO energy level is -3.02 eV, the LUMO energy level is -2.58 eV, and the bandgap is 0.44 eV; after randomly deleting one Na+ ion from DNA, the HOMO energy level and the LUMO energy level are -2.74 eV and -2.42 eV respectively, and the bandgap is 0.32 eV; it is worth mentioning that in the case of being electrically neutral, the HOMO energy levels in the vacuum environment and the aqueous environment are -3.02 eV and -5.07 eV respectively, which shows the influence of the solvent environment on the DNA energy level. And the electrical conductivity of the electrically neutral molecule is 4.07×10 -5 G0, and the change in electrical conductivity after deleting one Na+ is 4.69×10 -5 G0, an increase of 15%. And the change in the transmission rate of the two shows the same trend. In order to explore the change in the energy level, the two-dimensional DOS diagrams of the two are drawn.

[0064] Example 4

[0065] (1) Model construction: Download the crystal structure of the MAR70-DNA complex (PDB ID: 385d) from the RCSB website, then use GaussianView5.0 to delete the surrounding water molecules, and use Amber for energy minimization. Add Na+ ions to make the system electrically neutral to obtain a stable structure, and add hydrogen through GaussianView5.0, and upload the structure after adding hydrogen to the server.

[0066] (2) DFT Calculation: In this paper, the discrete Fourier transform and non-equilibrium Green's function are adopted, and the decoherence effect is considered. The DFT is studied by applying the B3LYP functional and the 6-31G(d, p) Gaussian 09 basis set. Here, we implicitly calculate the solvent effect using the polarizable continuum model. Subsequently, they are transformed into an orthogonal Hamiltonian matrix by the Löwdin transformation, and the corresponding results are obtained. On this basis, the decoherence method of non-equilibrium Green's function is used to calculate several important electrical signals in bare DNA.

[0067] (3) Calculating Parameters Related to Electrical Signals: Observe the influence of Na+ ions on the electrical properties of the crystal complex in an aqueous environment. First is the change in the energy band. When DNA is electrically neutral, the HOMO energy level of DNA is -4.61 eV, the LUMO energy level is -3.04 eV, and the bandgap is 1.57 eV; while after randomly deleting one Na+ ion from DNA, the HOMO energy level and LUMO energy level are -4.59 eV and -3.00 eV respectively, and the bandgap is 1.59 eV, with almost no change; and the electrical conductivity of the electrically neutral molecule is 1.27×10 -6 G0, and the change in electrical conductivity after deleting one Na+ is 2.09×10 -6 G0, showing a certain degree of increase.

[0068] (4) Observing the Change of Na+ Ions on Electrical Properties in a Vacuum Environment: When the complex crystal is electrically neutral, the HOMO energy level is -2.81 eV, the LUMO energy level is -1.63 eV, and the bandgap is 1.18 eV; while after randomly deleting one Na+ ion from DNA, the HOMO energy level and LUMO energy level are -2.67 eV and -1.75 eV respectively, and the bandgap is 0.92 eV; it is worth mentioning that in the case of both being electrically neutral, the HOMO energy levels in the vacuum environment and aqueous environment are -4.61 eV and -2.81 eV respectively, which shows the influence of the solvent environment on the DNA energy level. And the electrical conductivity of the electrically neutral molecule is 9.82×10 -7 G0, and the change in electrical conductivity after deleting one Na+ is 1.88×10 -6 G0. And the change in the transmission rate of the two shows the same trend. To explore the change in the energy level, the two-dimensional DOS diagrams of the two are plotted.

[0069] In summary, the present invention discloses a method for regulating the conductivity of DNA molecules. Through the calculation of the electrical properties of naked DNA and MAR70-DNA molecules in different solvent environments and in the presence of Na+, it is found that regardless of the solvent environment, the presence of Na+ affects the transport of charges at the lowest molecular occupied orbital, thereby reducing the transport rate and conductivity of the entire molecule. And when both molecules are kept electrically neutral, it is found that in a dry environment, the band gap of the molecule is greatly reduced and new energy levels are generated, thus changing the electrical properties of the molecule. Through the change of electrical properties, the present invention is expected to make an important contribution to the fabrication of DNA molecule sensors.

[0070] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the present technical solution, and they should all be covered by the scope of the claims of the present invention.

Claims

1. A method for regulating the conductivity of a drug-DNA complex based on a decoherence model, characterized in that: The following steps are involved: (a) constructing a target DNA molecule or a drug-DNA complex model, wherein the base sequence of the DNA molecule is CGATCG; (b) Adding a water box to the molecular or complex system constructed in step (a) and adjusting the Na + The number of ions makes the system electrically neutral; (c) placing the system of step (b) in a water environment or a vacuum environment, and removing at least one Na + Ions to change the charge state of the system; (d) Using density functional theory combined with the decoherent nonequilibrium Green's function method, the conductivity under different charge states or environments is calculated; (e) According to the conductivity calculation result of step (d), by adjusting the Na + The conductivity can be regulated by adjusting the number of ions or the solvent environment.

2. The method according to claim 1, characterized in that The method for constructing the DNA molecular model in step (a) is specifically as follows: The CGATCG sequence was input into NAB software to generate the initial structure file of B-type DNA. The initial structure file was imported into molecular dynamics software, the atomic force field and water force field were loaded, and the topology file and trajectory file were saved. The energy of the system was minimized to stabilize the structure.

3. The method according to claim 2, characterized in that: The drug is a MAR70 or Cyan drug molecule.

4. The method according to claim 3, characterized in that: In the step (a), the crystal structure of the complex containing MAR70 or Cyan is obtained from the PDB database, the surrounding water molecules are deleted and the structure is optimized; the drug and DNA molecular force field are loaded into the molecular dynamics software to generate the complex topology file and trajectory file; and the system is energy minimized to stabilize the structure.

5. The method according to claim 4, characterized in that In the step (b), Na + The number of ions added was 10, and the system stability was maintained by energy minimization.

6. The method according to claim 5, characterized in that The charge state is neutral or positively charged.

7. The method according to claim 6, characterized in that: In the step (b), the B3LYP functional and the 6-31G (d, p) basis set are used to perform DFT calculations to obtain the system Hamiltonian matrix; the Hamiltonian matrix is ​​corrected based on a decoherence model, and the solvent effect is simulated in combination with a polarization continuum model; and the conductivity and transmission rate are calculated by a non-equilibrium Green's function method.

8. The method according to claim 7, characterized in that Naked B-DNA molecules are regulated in the following ways: In a water environment, removing a Na + The conductivity of naked B-DNA can be increased from 1.30×10 -6 G0 increased to 2.82×10 -6 G0; In a vacuum, remove a Na + The conductivity of naked B-DNA can be increased from 1.27×10 -8 G0 increased to 2.95×10 -6 G0.

9. The method according to claim 8, characterized in that The conductivity adjustment range of the drug-DNA complex is: In the water environment of MAR70-DNA complex, one Na + After that, the conductivity increased from 4.51×10 -7 G0 changes to 1.19×10 -6 G0; In a vacuum environment, removing a Na + After that, the conductivity increased from 4.07×10 -5 G0 changes to 4.69×10 -5 G0; In the water environment of Cyan-DNA complex, one Na + After that, the conductivity increased from 1.27×10 -6 G0 increased to 2.09×10 -6 G0; In a vacuum environment, after removing one Na+ from the electrically neutral molecule, the conductivity increases from 9.82×10 -7 G0 changes to 1.88×10 -6 G0.

10. Use of the method according to any one of claims 1 to 9 for evaluating the binding efficiency of drug molecules to DNA.

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