CN115718086B - Characterization system and method of Aβ fluorescent probe dynamic fluorescence spectrum - Google Patents

Abstract

The invention provides a characterization system and a characterization method of an Abeta fluorescent probe dynamic fluorescence spectrum, and belongs to the field of protein detection. The invention discloses a representation system and a representation method of an Abeta fluorescent probe dynamic fluorescence spectrum, which are based on a multi-scale simulation method, adopt a technical route combining quantum chemical computation, molecular docking and molecular dynamics simulation and quantum mechanics/molecular mechanics calculation to realize accurate and rapid Abeta nano probe fluorescence spectrum simulation and prediction, carry out theoretical representation on a near infrared nano fluorescent probe real-time dynamic fluorescence spectrum of an Abeta plaque in a target organism, provide basis and reference for synthesizing a more efficient Alzheimer disease pathogenic protein diagnosis and treatment probe in the fields of biomedicine and the like, and are beneficial to early diagnosis and prevention of Alzheimer disease.

Description

A characterization system and method for dynamic fluorescence spectrum of Aβ fluorescent probe

Technical Field

The invention belongs to the field of protein detection, and in particular relates to a characterization system and method for dynamic fluorescence spectrum of Aβ fluorescent probe.

Background technique

The statements in this section merely provide background information related to the present invention and do not necessarily constitute prior art.

Alzheimer's disease (AD) is a neurodegenerative disease and the most common type of dementia in the elderly. The pathogenesis of Alzheimer's disease is still unclear. Among the various hypotheses proposed by scholars, the "amyloid cascade hypothesis" has been widely recognized. This hypothesis believes that amyloid deposition is the central link in the onset and development of AD. The imbalance between the patient's body's own clearance of amyloid and protein production induces the deposition of β-amyloid (Aβ) to form plaques, which in turn causes characteristic pathological changes such as synaptic damage, tau protein phosphorylation, and neuroinflammatory response, leading to neuronal function degeneration and loss. Since amyloid plaques are formed in the brain 20-30 years before the onset of related symptoms, they are considered to be marker proteins for AD. At first, people have always focused on the removal of amyloid plaques in the treatment of Alzheimer's disease. However, with the continuous deepening of research, many experimental results have confirmed that the removal of amyloid plaques can only relieve some symptoms, and cannot reverse pathological changes, and cannot achieve significant treatment and improvement of the disease. Therefore, removing the already formed amyloid plaques is not the primary goal of treating the disease, but preventing and early detecting amyloid deposition is more important. Designing and developing a series of probes for imaging amyloid plaques is critical for early diagnosis and prevention of the disease, and can also provide a powerful tool for further studying the pathological process of AD.

Among the technologies currently capable of imaging Aβ plaques, near-infrared fluorescence imaging has some obvious advantages, such as high sensitivity, no time consumption, strong penetration, and low background interference, which makes near-infrared fluorescence imaging very suitable for the detection of Aβ plaques in living organisms and the early diagnosis of AD. Therefore, the design and synthesis of safe and effective near-infrared fluorescent probes that target Aβ plaques in living organisms is of great significance for the monitoring of AD and improving the health of the elderly around the world.

In recent years, although a large number of near-infrared fluorescent probes targeting Aβ plaques have been synthesized experimentally, the characterization of the real-time dynamic spectrum of Aβ fluorescent probes is limited to a certain extent due to the complexity and variability of protein structure and the influence of external environmental fluctuations. This restricts the theoretical interpretation of the spectrum of nano-diagnostic probes and the effective development of targeted disease marker protein probes.

Summary of the invention

In order to overcome the above-mentioned deficiencies of the prior art, the present invention provides a system and method for characterizing the dynamic fluorescence spectrum of Aβ fluorescent probes, so as to achieve accurate and rapid simulation and prediction of the fluorescence spectrum of Aβ nanoprobes.

To achieve the above objectives, one or more embodiments of the present invention provide the following technical solutions:

In a first aspect, a method for characterizing a dynamic fluorescence spectrum of an Aβ fluorescent probe is disclosed, comprising:

Construct fluorescent probe molecules and optimize the probe structure using quantum chemical methods;

Extract the corresponding protein structure file from the protein database to obtain the structure of β-amyloid protein;

Based on the optimized fluorescent probe molecular configuration and the structure of β-amyloid protein, the fluorescent probe molecule is docked with β-amyloid protein to extract the most stable fluorescent probe molecule-β-amyloid protein complex conformation;

Molecular dynamics simulation was performed using the most stable fluorescent probe molecule-β-amyloid protein complex conformation as the initial configuration;

In the molecular dynamics simulation results, the configuration of the fluorescent probe molecule-β-amyloid protein complex was sampled at equal time intervals to obtain multiple sets of conformations;

Each group of conformations is divided into quantum mechanics and molecular mechanics regions, and the structure of the first excited state of the fluorescent probe molecule is optimized using quantum mechanics/molecular mechanics methods and the ONIOM model to obtain the fluorescence wavelength and intensity of the fluorescent probe molecule;

The fluorescence wavelength and intensity of each group of conformations were Lorentz broadened and summed to obtain the fluorescence spectrum.

A further technical solution, Lorentz broadening and summing, is as follows: the fluorescence wavelength and intensity of each group of conformations are calculated according to the formula:

Lorentz broadening is performed and the sum is taken, where ω is the wavelength on the horizontal axis of the spectrum, _fi and Ω _i represent the fluorescence intensity and wavelength of each group of conformations, respectively, and γ is the molecular energy level broadening, which is related to the energy level lifetime and is usually taken as a fixed value of 0.1 eV. Here the sum is taken over all conformations, that is, n represents the total number of conformations.

A further technical solution is to construct fluorescent probe molecules and optimize the probe structure using quantum chemical methods. Specifically, the fluorescent probe molecular structure is constructed with the help of GaussView6 visualization software, and the fluorescent probe molecular structure is optimized on the Gaussian16 software package using quantum chemical methods, B3LYP functional and 6-31G (d, p) basis set to obtain the most stable structure of the molecular system.

A further technical solution is to perform docking of the fluorescent probe molecule and the amyloid β protein, and the docking parameters are: the fluorescent probe molecule is set to be flexible, the amyloid β protein molecule is set to be rigid, the docking box size is 126×120×40, and the center of the box is located at the center of the amyloid β protein. The grid point spacing is taken as/> The number of docking conformations was 10.

A further technical solution is to extract the most stable fluorescent probe molecule-β-amyloid protein complex conformation as follows: based on the docking results, the absolute values of the binding energy of the ligand at different sites in the protein are counted, and the fluorescent probe molecule-β-amyloid protein complex conformation with the largest absolute value of binding energy is the most stable conformation, which can be extracted.

Further technical solutions, molecular dynamics simulation is specifically as follows:

Generate the topology file of the fluorescent probe molecule through the acpype command;

Use pdb2gmx to generate the topology file and gro file of amyloid beta protein;

Use genrestr command to generate restriction potential itp file of fluorescent probe molecule;

Use the editconf command to set a cube box with a side length of 1.0 nm and place the fluorescent probe molecule-β-amyloid protein complex in the center of the box;

Add water solvent to the box with the solvate command and add ions to the solution to neutralize it with the genion command;

After energy minimization and restrained dynamics simulations of the solution system, conventional dynamics simulations were performed.

A further technical solution is to divide the quantum mechanics and molecular mechanics regions as follows: GaussView6 software is used to divide each group of conformations into quantum mechanics and molecular mechanics regions, the fluorescent probe molecule is the quantum mechanics part, and its properties are calculated using quantum mechanics methods, and β-amyloid protein is the molecular mechanics part, and its structure is simulated using molecular mechanics methods; the structure of the first excited state of the fluorescent probe molecule is optimized using the quantum mechanics/molecular mechanics method and ONIOM model in the Gaussian 16 software package.

In a second aspect, a characterization system for dynamic fluorescence spectrum of Aβ fluorescent probe is disclosed, comprising:

A fluorescent probe molecule building module, which is configured to: construct fluorescent probe molecules and optimize the probe structure using quantum chemical methods;

A protein structure file extraction module is configured to: extract the corresponding protein structure file from the protein database to obtain the structure of β-amyloid protein;

A complex conformation extraction module, which is configured to: perform docking of the fluorescent probe molecule with the amyloid β protein based on the optimized fluorescent probe molecule configuration and the structure of the amyloid β protein, and extract the most stable fluorescent probe molecule-amyloid β protein complex conformation;

A molecular dynamics simulation module, which is configured to: perform molecular dynamics simulation using the most stable fluorescent probe molecule-β-amyloid protein complex conformation as an initial configuration;

A conformation extraction module is configured to: sample the configuration of the fluorescent probe molecule-β-amyloid protein complex at equal time intervals in the molecular dynamics simulation results to obtain multiple groups of conformations;

A fluorescence wavelength and intensity acquisition module is configured to: divide each group of conformations into quantum mechanics and molecular mechanics regions, optimize the structure of the first excited state of the fluorescent probe molecule using quantum mechanics/molecular mechanics methods and the ONIOM model, and obtain the fluorescence wavelength and intensity of the fluorescent probe molecule;

The fluorescence spectrum characterization module is configured to perform Lorentz broadening on the fluorescence wavelength and intensity of each group of conformations and sum them up to obtain the fluorescence spectrum.

A further technical solution is to divide the quantum mechanics and molecular mechanics regions as follows: GaussView 6 is used to divide each group of conformations into regions, where the fluorescent probe molecules are used as the quantum mechanics part, and their properties are calculated using quantum mechanics methods, and the β-amyloid protein is used as the molecular mechanics part, and its structure is simulated using molecular mechanics methods.

A further technical solution, Lorentz broadening and summing, is specifically as follows: the fluorescence wavelength and intensity of each group of conformations are Lorentz broadened and summed according to the following formula to obtain the fluorescence spectrum;

Among them, ω is the wavelength on the horizontal axis of the spectrum, _fi and Ω _i represent the fluorescence intensity and wavelength of each group of conformations respectively, γ is the molecular energy level broadening, which is related to the energy level lifetime and usually takes a fixed value of 0.1eV. The summation here is taken over all conformations, that is, n represents the total number of conformations.

In a third aspect, a computer device is disclosed, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor implements the steps of the above method when executing the program.

In a fourth aspect, a computer-readable storage medium stores a computer program, which performs the steps of the above method when executed by a processor.

One or more of the above technical solutions have the following beneficial effects:

The present invention discloses a characterization system and method for the dynamic fluorescence spectrum of an Aβ fluorescent probe. The system and method are based on a multi-scale simulation method and adopt a technical route combining quantum chemical calculation, molecular docking and molecular dynamics simulation as well as quantum mechanics/molecular mechanics calculation to achieve accurate and rapid simulation and prediction of the fluorescence spectrum of the Aβ nanoprobe, and theoretically characterize the real-time dynamic fluorescence spectrum of the near-infrared nanofluorescent probe targeting the Aβ plaques in the organism, thereby providing a basis and reference for the synthesis of more efficient Alzheimer's disease pathogenic protein diagnostic and therapeutic probes in the biomedical field and other fields, and facilitating the early diagnosis and prevention of Alzheimer's disease.

Advantages of additional aspects of the present invention will be given in part in the following description, and in part will become obvious from the following description, or will be learned through practice of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

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.

FIG1 is a flowchart of an implementation of Example 1 of the present invention;

FIG2 is a schematic diagram of the molecular structure of the fluorescent probe in Example 1 of the present invention;

FIG3 is a schematic diagram of the division of regions in the quantum mechanics/molecular mechanics method in Example 1 of the present invention;

FIG4 is a comparison of the fluorescence spectrum obtained based on the present invention in Example 1 of the present invention with the calculation results based on first principles and the experimental measurement results.

Detailed ways

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

It should be noted that the terms used herein are for describing specific embodiments only and are not intended to be limiting of exemplary embodiments according to the present invention.

In the absence of conflict, the embodiments of the present invention and the features of the embodiments may be combined with each other.

Terminology explanation:

Aβ: Aβ, also known as amyloidβ-protein, has a molecular weight of about 4kDa. It is hydrolyzed from β-amyloid precursor protein (APP) and secreted by cells. It has strong neurotoxic effects after precipitation and accumulation in the cell matrix. The deposition of Aβ is not only related to neuronal degeneration, but also can activate a series of pathological events, including the activation of astrocytes and microglia, the destruction of the blood-brain barrier and changes in microcirculation. It is the main cause of neuronal degeneration and death around senile plaques in Alzheimer's patients.

Embodiment 1

This embodiment discloses a method for characterizing the dynamic fluorescence spectrum of an Aβ fluorescent probe, comprising:

Step 1: Optimization of the molecular structure of the fluorescent probe

The fluorescent probe molecule shown in Figure 2 was selected as the research object. The fluorescent probe molecular structure was constructed with the help of GaussView 6 visualization software, and the ground state of the constructed molecular system was optimized using the Gaussian 16 software package to obtain the most stable structure of the molecular system. Quantum chemical methods, B3LYP functionals and 6-31G (d, p) basis sets were used for optimization.

Step 2: Simulation of the docking process between the fluorescent probe molecule and β-amyloid protein

The structure of amyloid β was obtained by downloading the amyloid β structure file from the Protein Data Bank (https://www.pdbus.org/) according to the PDB ID keyword 5OQV.

Based on the optimized fluorescent probe molecular configuration and the structure of β-amyloid protein, the open source Autodock molecular simulation software was further used to perform docking of the fluorescent probe molecule and β-amyloid protein. The docking parameters were set as follows: the fluorescent probe molecule was set to be flexible, the protein molecule was set to be rigid, the docking box size was 126×120×40, and the center of the box was located at the center of β-amyloid protein. The grid point spacing is taken as/> The docking method was set to Lamrckian GA 4.2, and the number of docking conformations was chosen to be 10 by default.

Step 3: Based on the docking results, the absolute values of the binding energy of the ligand at different sites in the protein are calculated. The fluorescent probe molecule-β-amyloid protein complex conformation with the largest absolute value of binding energy is the most stable conformation and is extracted.

Step 4: Using the most stable conformation of the fluorescent probe molecule-β-amyloid protein complex obtained in the above step as the initial configuration, a molecular dynamics simulation of the fluorescent probe molecule-β-amyloid protein complex is performed. The specific contents are as follows:

Generate the topology file of the fluorescent probe molecule through the acpype command;

Use pdb2gmx to generate the topology file and gro file of amyloid beta protein;

Use genrestr command to generate restriction potential itp file of fluorescent probe molecule;

Use the editconf command to set a cube box with a side length of 1.0 nm and place the fluorescent probe molecule-β-amyloid protein complex in the center of the box;

Add water solvent to the box with the solvate command and add ions to the solution to neutralize it with the genion command;

After energy minimization and 100 ps of confined dynamics simulations of the solution system, conventional dynamics simulations were performed with a simulation time of 10 ns.

Step 5: In the molecular dynamics simulation results, the configuration of the fluorescent probe molecule-β-amyloid protein complex is sampled at equal time intervals every 5 ps to obtain 2000 sets of conformations.

Step 6: Use GaussView 6 to divide each group of conformations into two parts (as shown in Figure 3), where the fluorescent probe molecule is the quantum mechanics part, and its properties are calculated using accurate and expensive quantum mechanics methods; beta-amyloid protein is the molecular mechanics part, and its structure is simulated using molecular mechanics methods with lower accuracy but higher efficiency. The structure of the first excited state of the fluorescent probe molecule is optimized using the quantum mechanics/molecular mechanics method and ONIOM model in the Gaussian 16 software package to obtain the fluorescence wavelength and intensity of the fluorescent probe molecule.

Step 7: The fluorescence wavelength and intensity of the fluorescent probe molecule in β-amyloid protein are calculated according to the formula

The fluorescence spectrum is obtained by performing Lorentz broadening and summing (as shown in Figure 4), where ω is the wavelength on the horizontal axis of the spectrum, _fi and Ω _i represent the fluorescence intensity and wavelength of each group of conformations, respectively, and γ is the molecular energy level broadening, which is related to the energy level lifetime and is usually taken as a fixed value of 0.1 eV. The summation is taken over all conformations, that is, n represents the total number of conformations.

Embodiment 2

A characterization system for dynamic fluorescence spectrum of Aβ fluorescent probe, comprising:

The fluorescent probe molecular construction module is configured as follows: constructing the fluorescent probe molecular structure with the help of GaussView6 visualization software, and optimizing the molecular structure on the Gaussian16 software package using quantum chemistry methods, B3LYP functional and 6-31G (d, p) basis set to obtain the most stable structure of the molecular system;

A protein structure file extraction module is configured to: extract the corresponding protein structure file from the protein database to obtain the structure of β-amyloid protein;

The complex conformation extraction module is configured as follows: based on the optimized fluorescent probe molecular configuration and the structure of β-amyloid protein, the open source Autodock molecular simulation software is used to perform docking of the fluorescent probe molecule and β-amyloid protein, and based on the docking results, the binding energy values of the ligand at different sites in the protein are counted, and the fluorescent probe molecule-β-amyloid protein complex conformation with the largest absolute value of binding energy is extracted as the most stable conformation;

A molecular dynamics simulation module, which is configured to: perform molecular dynamics simulation using the most stable fluorescent probe molecule-β-amyloid protein complex conformation as an initial configuration;

A conformation extraction module is configured to: sample the configuration of the fluorescent probe molecule-β-amyloid protein complex at equal time intervals in the molecular dynamics simulation results to obtain multiple groups of conformations;

The fluorescence wavelength and intensity acquisition module is configured as follows: using GaussView6 software to divide each group of conformations into quantum mechanics and molecular mechanics regions, wherein the fluorescent probe molecule is used as the quantum mechanics part, and its properties are calculated using an accurate and expensive quantum mechanics method; β-amyloid protein is used as the molecular mechanics part, and its structure is simulated using a molecular mechanics method with lower accuracy but higher efficiency; using the Gaussian 16 software package to optimize the structure of the first excited state of the fluorescent probe molecule using the quantum mechanics/molecular mechanics method and the ONIOM model, and obtaining the fluorescence wavelength and intensity of the fluorescent probe molecule;

The fluorescence spectrum characterization module is configured to perform Lorentz broadening on the fluorescence wavelength and intensity of each group of conformations according to the following formula and add them up to obtain the fluorescence spectrum.

Among them, ω is the wavelength on the horizontal axis of the spectrum, _fi and Ω _i represent the fluorescence intensity and wavelength of each group of conformations respectively, and γ is the molecular energy level broadening, which is related to the energy level lifetime and usually takes a fixed value of 0.1eV. The sum here is taken over all conformations, that is, n represents the total number of conformations.

Embodiment 3

The purpose of this embodiment is to provide a computer device, including a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor implements the steps of the above method when executing the program.

Embodiment 4

The purpose of this embodiment is to provide a computer-readable storage medium.

A computer-readable storage medium stores a computer program, which executes the steps of the above method when executed by a processor.

The steps involved in the above embodiments 3 and 4 correspond to the method embodiment 1. For the specific implementation, please refer to the relevant description part of embodiment 1. The term "computer-readable storage medium" should be understood as a single medium or multiple media including one or more instruction sets; it should also be understood to include any medium that can store, encode or carry an instruction set for execution by a processor and enable the processor to execute any method in the present invention.

Those skilled in the art should understand that the modules or steps of the present invention described above can be implemented by a general-purpose computer device, or alternatively, they can be implemented by a program code executable by a computing device, so that they can be stored in a storage device and executed by the computing device, or they can be made into individual integrated circuit modules, or multiple modules or steps therein can be made into a single integrated circuit module for implementation. The present invention is not limited to any specific combination of hardware and software.

Although the above describes the specific implementation mode of the present invention in conjunction with the accompanying drawings, it is not intended to limit the scope of protection of the present invention. Technical personnel in the relevant field should understand that various modifications or variations that can be made by technical personnel in the field without creative work on the basis of the technical solution of the present invention are still within the scope of protection of the present invention.

Claims (11)

1. A characterization method of an Abeta fluorescent probe dynamic fluorescence spectrum is characterized by comprising the following steps:

Constructing fluorescent probe molecules and optimizing the probe structure by adopting a quantum chemical method;

Extracting corresponding protein structure files from a protein database to obtain the structure of beta amyloid;

Based on the optimized fluorescent probe molecular configuration and the structure of the beta amyloid, performing docking of the fluorescent probe molecules and the beta amyloid, and extracting the most stable fluorescent probe molecule-beta amyloid complex conformation;

performing molecular dynamics simulation by taking the most stable fluorescent probe molecule-beta amyloid complex conformation as an initial configuration;

sampling the fluorescent probe molecule-beta amyloid complex configuration at equal time intervals in a molecular dynamics simulation result to obtain a multi-group conformation;

Dividing each group of images into quantum mechanics and molecular mechanics areas, and optimizing the structure of a first excited state of the fluorescent probe molecule by using a quantum mechanics/molecular mechanics method and ONIOM model to obtain the fluorescent wavelength and intensity of the fluorescent probe molecule;

The fluorescence wavelengths and intensities of each group of images are Lorentzian stretched and summed to obtain a fluorescence spectrum.

2. The method for characterizing dynamic fluorescence spectrum of aβ fluorescent probe according to claim 1, wherein lorentz stretching and summing is specifically: the fluorescence wavelength and intensity of each group of the image were formulated as:

Lorentz stretching and summing is performed, where ω is the wavelength on the spectral abscissa, f _i and Ω _i represent the fluorescence intensity and wavelength, respectively, of each group of conformations, γ is the molecular level stretching, and n represents the total number of conformations.

3. The characterization method of the aβ fluorescent probe dynamic fluorescence spectrum of claim 1 wherein constructing fluorescent probe molecules and optimizing the probe structure by quantum chemistry methods is specifically: the molecular structure of the fluorescent probe is constructed by means of GaussView visual software, and the molecular structure of the fluorescent probe is optimized on a Gaussian16 software package by adopting a quantum chemical method, a B3LYP functional and a 6-31G (d, p) group, so that the most stable structure of a molecular system is obtained.

4. The method for characterizing dynamic fluorescence spectrum of aβ fluorescent probe according to claim 1, wherein the docking parameters when performing docking of fluorescent probe molecules and β amyloid are: the fluorescent probe molecule is flexible, the beta amyloid molecule is rigid, the size of the butt joint box is 126 multiplied by 120 multiplied by 40, and the center of the box is positioned at the center of the beta amyloidWhere lattice spacing is taken as/>The number of docking conformations was 10.

5. The method for characterizing a dynamic fluorescence spectrum of an aβ fluorescent probe according to claim 1, wherein said extracting the most stable fluorescent probe molecule- β amyloid complex conformation is specifically: based on the docking result, calculating the absolute value of binding energy of the ligand at different sites in the protein, and extracting the fluorescent probe molecule-beta amyloid complex conformation with the maximum absolute value of binding energy from the most stable conformation.

6. The method for characterizing dynamic fluorescence spectrum of aβ fluorescent probe of claim 1 wherein said molecular dynamics simulation is specifically:

Generating a topology file of fluorescent probe molecules by acpype commands;

generating a topology file and a gro file of beta amyloid protein with pdb2 gmx;

A file of restriction potential itp for fluorescent probe molecules generated with genrestr commands;

a editconf order is used to set a square box with a side length of 1.0nm, and a fluorescent probe molecule-beta amyloid complex is placed at the right center of the box;

Adding an aqueous solvent to the cassette by solvate command and adding ions to the solution to neutralize the solution by genion command;

After energy minimization and limiting kinetic simulation of the solution system, conventional kinetic simulation was performed.

7. The method for characterizing dynamic fluorescence spectrum of aβ fluorescent probe according to claim 1, wherein said dividing of quantum mechanical and molecular mechanical regions is specifically: and carrying out quantum mechanics and molecular mechanics region division on each group of images by utilizing GaussView software, calculating the properties of the fluorescent probe molecules by using a quantum mechanics method, using beta amyloid protein as a molecular mechanics part, and simulating the structure of the fluorescent probe molecules by using a molecular mechanics method.

8. A characterization system for dynamic fluorescence spectrum of an aβ fluorescent probe, comprising:

a fluorescent probe molecule building block configured to: constructing fluorescent probe molecules and optimizing the probe structure by adopting a quantum chemical method;

A protein structure file extraction module configured to: extracting corresponding protein structure files from a protein database to obtain the structure of beta amyloid;

A complex conformational extraction module configured to: based on the optimized fluorescent probe molecular configuration and the structure of the beta amyloid, performing docking of the fluorescent probe molecules and the beta amyloid, and extracting the most stable fluorescent probe molecule-beta amyloid complex conformation;

A molecular dynamics simulation module configured to: performing molecular dynamics simulation by taking the most stable fluorescent probe molecule-beta amyloid complex conformation as an initial configuration;

a constellation extraction module configured to: sampling the fluorescent probe molecule-beta amyloid complex configuration at equal time intervals in a molecular dynamics simulation result to obtain a multi-group conformation;

A fluorescence wavelength and intensity acquisition module configured to: dividing each group of images into quantum mechanics and molecular mechanics areas, and optimizing the structure of a first excited state of the fluorescent probe molecule by using a quantum mechanics/molecular mechanics method and ONIOM model to obtain the fluorescent wavelength and intensity of the fluorescent probe molecule;

a fluorescence spectrum characterization module configured to: the fluorescence wavelengths and intensities of each group of images are Lorentzian stretched and summed to obtain a fluorescence spectrum.

9. The characterization system of claim 8 wherein the division of the quantum mechanical and molecular mechanical regions is: carrying out regional division on each group of images by utilizing GaussView, wherein fluorescent probe molecules are used as quantum mechanical parts, calculating the properties of the fluorescent probe molecules by using a quantum mechanical method, and simulating the structure of the fluorescent probe molecules by using a molecular mechanical method, wherein beta amyloid is used as a molecular mechanical part;

Or, the lorentz stretching and summing is specifically as follows: carrying out Lorentz stretching on the fluorescence wavelength and the intensity of each group of images according to the following formula, and summing to obtain a fluorescence spectrum;

where ω is the wavelength on the spectral abscissa, f _i and Ω _i represent the fluorescence intensity and wavelength, respectively, of each group of conformations, γ is the molecular level broadening, and n represents the total number of conformations.

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 implements the steps of the method of any of claims 1-7 when the program is executed.

11. A computer readable storage medium, characterized in that a computer program is stored thereon, which program, when being executed by a processor, performs the steps of the method according to any of claims 1-7.