Traditional Chinese medicine prescription targeted screening and recycling technology based on natural compounds and target structures

Abstract

The invention relates to the field of medicine screening methods, and discloses a traditional Chinese medicine prescription targeted screening and recycling technology based on natural compounds and target structures, which comprises the following steps: establishing a traditional Chinese medicine prescription database which comprises composition, efficacy, major functions, sources and historical application records of traditional Chinese medicine prescriptions; establishing a database of the natural compounds, wherein the database contains chemical structures, physicochemical properties, biological activities, source plants or organisms, extraction methods and known pharmacological actions of the natural compounds; and establishing a target spot structure database. By establishing a traditional Chinese medicine prescription database, a natural compound database and a target structure database, a natural compound with high affinity with a target structure can be accurately identified. The precise screening mode breaks through the limitation that traditional Chinese medicine prescriptions depend on experience and fuzzy theories, so that the composition of the traditional Chinese medicine prescriptions is more scientific and reasonable, and the medicine effect is clearer.

Description

Technical Field

[0001] This invention relates to the field of drug screening methods, specifically a targeted screening and reuse technology for traditional Chinese medicine prescriptions based on natural compounds and target structures. Background Technology

[0002] Traditional Chinese medicine (TCM), as an important component of traditional Chinese medicine, plays a vital role in disease prevention and treatment with its unique theoretical system and rich clinical experience. Traditional TCM prescriptions are largely based on TCM theory and clinical experience, and their efficacy is widely recognized. However, the composition and application of traditional TCM prescriptions often rely on empirical judgment, lacking clear molecular mechanisms and target information, which to some extent limits the modernization and internationalization of TCM. Furthermore, the traditional TCM research and development process is typically time-consuming, costly, and has a low success rate, making it difficult to meet the requirements of modern medicine for drug precision and efficiency.

[0003] In recent years, with the rapid development of computer technology and bioinformatics, computer-aided drug design (CADD) technology has been gradually applied to the field of traditional Chinese medicine research. CADD technology, through methods such as molecular docking, molecular dynamics simulations, and pharmacophore models, can predict the interaction between compounds and targets at the molecular level, providing an efficient and rapid means for drug screening. However, the current application of CADD technology in the field of traditional Chinese medicine still has limitations, mainly focusing on the screening of single compounds, lacking a holistic consideration of traditional Chinese medicine compound formulas, and failing to reflect the synergistic effects and complexity of these formulas.

[0004] Furthermore, the development and utilization of traditional Chinese medicine (TCM) resources also face challenges. Despite the rich diversity of TCM resources, many natural products with potential medicinal value have not yet been fully studied and applied. On the one hand, the lack of systematic database support leads to scattered resource information, making efficient screening and utilization difficult; on the other hand, research on the chemical composition and pharmacological effects of TCM resources is not in-depth enough, making it difficult to provide a scientific basis for their sustainable development.

[0005] In summary, existing technologies still have shortcomings in the precise screening of traditional Chinese medicine (TCM) prescriptions, improving R&D efficiency, and rationally utilizing resources. Therefore, there is an urgent need for a new technology that combines traditional Chinese medicine theory with modern science and technology to achieve precise screening and reuse of TCM prescriptions. This invention addresses this need by proposing a targeted screening and reuse technology for traditional Chinese medicine prescriptions based on natural compounds and target structures. The aim is to establish a systematic database and utilize advanced computer-aided drug design technology, combined with in vitro and in vivo experimental verification, to achieve precise optimization and efficient development of TCM prescriptions, while simultaneously promoting the rational utilization and sustainable development of TCM resources. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a targeted screening and reuse technology for traditional Chinese medicine prescriptions based on natural compounds and target structures, thus solving the problems mentioned in the background section.

[0007] To achieve the above objectives, the present invention provides the following technical solution: a targeted screening and reuse technology for traditional Chinese medicine prescriptions based on natural compounds and target structures, comprising the following steps:

[0008] Establish a traditional Chinese medicine prescription database, which includes the composition, efficacy, indications, source, and historical application records of traditional Chinese medicine prescriptions;

[0009] Establish a database of natural compounds, which includes the chemical structure, physicochemical properties, biological activities, source plant or organism, extraction method, and known pharmacological effects of natural compounds;

[0010] Establish a target structure database, which includes the three-dimensional structure, biological activity, mechanism of action, disease correlation, and known ligand information of the target;

[0011] Using computer-aided drug design technology, combined with molecular docking, molecular dynamics simulation and pharmacophore model, we can target and screen natural compounds in traditional Chinese medicine prescriptions to identify natural compounds with high affinity for the target structure and record their binding sites and modes of action.

[0012] The screened natural compounds were validated in vitro, including cell activity assays, enzyme activity assays, and target affinity assays, to determine their activity and specificity for the target structure.

[0013] Calculate and rank compounds based on their priority scores, which are determined by parameters such as bioactivity and ADMET properties.

[0014] The compounds are scored based on parameters such as bioactivity and ADMET properties, and their priorities are calculated and ranked. Using the candidate compounds with good ADMET properties that have been screened, the set of herbs containing these compounds is searched in reverse. The herb scores are calculated and ranked based on the compound priority scores, thereby obtaining the herb set.

[0015] Prescriptions are derived and scored from a set of herbs, and related traditional prescriptions are searched for based on the obtained herb set. Then, the found prescriptions are scored and ranked according to the herb scores to identify candidate prescriptions.

[0016] The optimized traditional Chinese medicine prescriptions were validated in vivo through experiments, including animal model experiments, to evaluate their therapeutic effects and safety for specific diseases.

[0017] Based on the experimental results, the application of traditional Chinese medicine prescriptions in the treatment of specific diseases was determined, and quality control standards and production processes were established.

[0018] Based on in vitro experimental results and combined with the compatibility theory of traditional Chinese medicine prescriptions, the traditional Chinese medicine prescriptions were optimized by adjusting the drug composition, dosage, or adding new drug components to improve their targeting of the target structure and to verify the comprehensive activity of the optimized prescriptions on the target.

[0019] Preferably, the prescriptions in the traditional Chinese medicine prescription database are derived from classic Chinese medicine literature and are organized and classified in conjunction with modern clinical application cases.

[0020] Preferably, the compounds in the natural compound database include natural products extracted from plants, animals, and microorganisms, as well as derivatives obtained through chemical modification, and the structural information of each compound is confirmed by high-resolution mass spectrometry and nuclear magnetic resonance technology.

[0021] Preferably, the targets in the target structure database include biological macromolecules such as proteins, nucleic acids, and enzymes, whose three-dimensional structures are obtained by X-ray crystallography, nuclear magnetic resonance spectroscopy, or cryo-electron microscopy, and the bioactivity of each target is verified by in vitro experiments and literature reviews.

[0022] Preferably, the computer-aided drug design technology includes:

[0023] Molecular docking software was used to preliminarily screen natural compounds and target structures, calculate binding energies, and predict binding sites.

[0024] The stability of the selected natural compounds and target complexes was evaluated by molecular dynamics simulations, with a simulation time of no less than 100 nanoseconds.

[0025] Based on the pharmacophore model, the active groups of natural compounds are analyzed, and the screening conditions are optimized to improve screening efficiency and accuracy.

[0026] Depending on the intended use of the drug, ADMETs should be screened. For example, topical medications need to be screened for transdermal absorption potential and skin irritation, while oral medications need to be screened for oral absorption rate.

[0027] Preferably, the in vitro experimental verification includes:

[0028] Cell viability assays were performed to evaluate the effects of natural compounds on cell proliferation using the MTT or CCK-8 assays.

[0029] Enzyme activity assays use colorimetric or fluorescence methods to determine the inhibitory or activating effects of natural compounds on the activity of target enzymes.

[0030] Target affinity experiments were conducted by determining the binding constant between the natural compound and the target using surface plasmon resonance technology or isothermal titration calorimetry.

[0031] Preferably, the in vivo experimental verification includes:

[0032] Construct animal models associated with specific diseases, such as cardiovascular disease models, tumor models, or nervous system disease models;

[0033] The therapeutic effects of the optimized traditional Chinese medicine prescription on animal models were evaluated, including pathological indicators, recovery of physiological functions, and survival rate.

[0034] The safety of the prescription is assessed through toxicological experiments, including acute toxicity, chronic toxicity, and pharmacokinetic studies.

[0035] Preferably, the optimized traditional Chinese medicine prescription is used in the treatment of specific diseases such as cardiovascular diseases, tumors, and nervous system diseases, including but not limited to prevention, treatment, and adjuvant therapy.

[0036] Preferably, the complex of the screened natural compound and the target structure can be used for target validation, drug design templates, and drug screening targets in drug development. The structural information of the complex is analyzed using high-resolution technology and used to guide the subsequent optimization and development of drugs.

[0037] This invention provides a targeted screening and reuse technology for traditional Chinese medicine prescriptions based on natural compounds and target structures. It has the following beneficial effects:

[0038] 1. This invention establishes a database of traditional Chinese medicine prescriptions, a database of natural compounds, and a database of target structures. By utilizing computer-aided drug design technology for targeted screening of natural compounds, it can accurately identify natural compounds with high affinity for target structures. This precise screening method overcomes the limitations of traditional Chinese medicine prescriptions, which rely on experience and fuzzy theory, making the composition of Chinese medicine prescriptions more scientific and rational, and the drug effects more clearly defined.

[0039] 2. This invention combines modern computer technology and experimental verification methods, greatly improving research and development efficiency. In the computer-aided drug design stage, methods such as molecular docking, molecular dynamics simulation, and pharmacophore models can be used to virtually screen a large number of natural compounds in a short time, quickly narrowing the research scope and reducing unnecessary experimental work. Subsequent in vitro and in vivo experimental verification is also more targeted, enabling rapid determination of the efficacy and safety of traditional Chinese medicine prescriptions.

[0040] 3. This technology, through targeted screening and reuse of traditional Chinese medicine prescriptions, can deeply explore the potential value of Chinese medicinal resources, enabling the re-evaluation and application of some previously overlooked or underutilized resources. Simultaneously, in-depth research on natural compounds can provide a better understanding of the chemical composition and pharmacological effects of Chinese medicinal resources, offering a scientific basis for their sustainable development. Attached Figure Description

[0041] Figure 1 This is a flowchart of the present invention. Detailed Implementation

[0042] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0043] Example:

[0044] Please see the appendix Figure 1 This invention provides a technology for targeted screening and reuse of traditional Chinese medicine prescriptions based on natural compounds and target structures, comprising the following steps:

[0045] Establish a traditional Chinese medicine prescription database, which includes the composition, efficacy, indications, source, and historical application records of traditional Chinese medicine prescriptions. The prescriptions in the traditional Chinese medicine prescription database are derived from classic Chinese medicine literature and are organized and classified in conjunction with modern clinical application cases.

[0046] A database of natural compounds was established, which includes the chemical structure, physicochemical properties, biological activities, source plant or organism, extraction method, and known pharmacological effects of natural compounds. The compounds in the database include natural products extracted from plants, animals, and microorganisms, as well as derivatives obtained through chemical modification, and the structural information of each compound was confirmed by high-resolution mass spectrometry and nuclear magnetic resonance technology.

[0047] Specifically, the composition information of traditional Chinese medicine prescriptions includes the name, dosage, and processing method of each herb in the prescription. Each herb has its specific dosage and processing requirements, and this information is recorded in detail in the database for subsequent analysis of its compatibility and efficacy contributions. The prescriptions also describe in detail the therapeutic effects of the herbs, such as relieving exterior syndromes, clearing heat, purging, eliminating dampness, resolving phlegm, regulating qi, regulating blood, tonifying, calming the mind, opening the orifices, astringing, and expelling parasites. The sources of the prescriptions are recorded, including ancient classic medical books such as the *Huangdi Neijing*, *Shanghan Zabing Lun*, and *Jinkui Yaolue*, as well as modern clinical research literature and expert experience summaries.

[0048] A target structure database was established, which includes the three-dimensional structure, biological activity, mechanism of action, disease correlation, and known ligand information of the targets. The targets in the target structure database include biological macromolecules such as proteins, nucleic acids, and enzymes. Their three-dimensional structures were obtained by X-ray crystallography, nuclear magnetic resonance spectroscopy, or cryo-electron microscopy, and the biological activity of each target was verified by in vitro experiments and literature review.

[0049] Computer-aided drug design techniques, combined with molecular docking, molecular dynamics simulations, and pharmacophore models, are used to target and screen natural compounds in traditional Chinese medicine prescriptions. This process identifies natural compounds with high affinity for the target structure and records their binding sites and modes of action. The computer-aided drug design techniques include:

[0050] Molecular docking software was used to preliminarily screen natural compounds and target structures, calculate binding energies, and predict binding sites.

[0051] Calculate and rank compounds based on their priority scores, which are determined by parameters such as bioactivity and ADMET properties.

[0052] Specifically, calculating and ranking compounds based on priority scores is a crucial step, aiming to comprehensively evaluate compounds based on key parameters such as bioactivity and ADMET (absorption, distribution, metabolism, excretion, and toxicity) characteristics. This process involves quantifying the performance of each compound across multiple dimensions, where bioactivity reflects the compound's ability to bind to the target and its potential therapeutic effect, while ADMET characteristics predict the compound's pharmacokinetic behavior and safety in the human body. By calculating a comprehensive score for each compound, those most likely to become successful drug candidates can be effectively identified and prioritized, thereby guiding subsequent drug development and experimental research, ensuring that resources are concentrated on the most promising compounds.

[0053] The compounds are scored based on parameters such as bioactivity and ADMET properties, and their priorities are calculated and ranked. Using the candidate compounds with good ADMET properties that have been screened, the set of herbs containing these compounds is searched in reverse. The herb scores are calculated and ranked based on the compound priority scores, thereby obtaining the herb set.

[0054] Prescriptions are derived and scored from a set of herbs, and related traditional prescriptions are searched for based on the obtained herb set. Then, the found prescriptions are scored and ranked according to the herb scores to identify candidate prescriptions.

[0055] Based on the experimental results, the application of traditional Chinese medicine prescriptions in the treatment of specific diseases was determined, and quality control standards and production processes were established.

[0056] Based on in vitro experimental results and combined with the compatibility theory of traditional Chinese medicine prescriptions, the traditional Chinese medicine prescriptions were optimized by adjusting the drug composition, dosage, or adding new drug components to improve their targeting of the target structure and to verify the comprehensive activity of the optimized prescriptions on the target.

[0057] Specifically, by establishing a many-to-many correspondence between herbs and their active ingredients, a systematic analysis of each component in a traditional Chinese medicine (TCM) prescription was achieved. Using computer-aided drug design (CADD) technology, molecular docking, molecular dynamics simulations, and pharmacophore modeling were performed on these active ingredients to screen candidate compounds with high affinity for specific target structures. Subsequently, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of these candidate compounds were predicted and analyzed to assess their potential for drug development. Candidate compounds with good ADMET properties were used to back-search for sets of herbs containing these compounds, and then, based on these sets of herbs, to back-search for related traditional TCM prescriptions. By constructing a TCM traditional prescription ranking algorithm based on herb sets, traditional prescriptions were scored and ranked, thereby identifying candidate prescriptions with optimal ADMET properties and the highest therapeutic potential, providing a scientific basis and technical support for the modernization of TCM and the development of new drugs.

[0058] This invention further provides a traditional Chinese medicine prescription ranking algorithm based on herbal collections. This algorithm systematically scores and ranks traditional Chinese medicine prescriptions by comprehensively considering the efficacy, safety, historical application records, and affinity of herbs for specific targets. The algorithm includes the following steps:

[0059] Efficacy evaluation: Using computer-aided drug design technology, the interaction between the active ingredients in herbal medicines and disease-related targets is simulated to evaluate their potential efficacy.

[0060] Safety analysis: The safety of active ingredients in herbs is assessed using the ADMET prediction model, including absorption, distribution, metabolism, excretion, and toxicity.

[0061] Historical application record analysis: By referring to the historical application records in the traditional Chinese medicine prescription database, we analyze the application and efficacy of herbs in history.

[0062] Affinity score: The affinity between the active ingredients in the herbal medicine and the target is scored based on the results of molecular docking and molecular dynamics simulations.

[0063] Overall score: The scores from the above items are weighted and combined to form an overall score for each prescription.

[0064] Sorting: All prescriptions are sorted according to the overall score, and prescriptions with higher scores are selected as candidate prescriptions.

[0065] The stability of the selected natural compounds and target complexes was evaluated by molecular dynamics simulations, with a simulation time of no less than 100 nanoseconds.

[0066] Specifically, molecular docking is primarily used to predict the binding modes and binding affinities between small molecule compounds (such as natural compounds) and biological macromolecular targets (such as proteins and nucleic acids). Using molecular docking software, the three-dimensional structure of a natural compound can be matched with the target structure, and the binding energy between them can be calculated, thereby assessing the strength of their interaction. A lower binding energy indicates a higher binding affinity between the compound and the target. Furthermore, molecular docking can predict the binding sites of compounds within the target structure, helping researchers understand the details of the interaction between the compound and the target. For example, molecular docking can reveal that certain natural compounds can bind tightly to the active or allosteric sites of target proteins, thereby exerting pharmacological effects.

[0067] Molecular dynamics simulations, based on Newton's laws of motion, are computational methods used to study the dynamic behavior and stability of biomolecules in solution environments. In this invention, molecular dynamics simulations are used to further evaluate the complexes of natural compounds screened through molecular docking with target sites. The simulation time is no less than 100 ns to ensure sufficient observation of the dynamic changes of the complexes under physiological conditions. Molecular dynamics simulations can provide important information about the stability of the complexes, such as the residence time of the compound at the target binding site, conformational changes at the binding site, and the influence of solvent molecules on the stability of the complexes. By analyzing this dynamic information, the stability of the interaction between the compound and the target site can be determined more accurately, thereby screening for candidate compounds with high stability.

[0068] The active groups of natural compounds are analyzed based on pharmacophore models to optimize screening conditions and improve screening efficiency and accuracy. ADMETs are screened according to their intended use; for example, topical medications require screening for transdermal absorption potential and skin irritation, while oral medications require screening for oral absorption rates.

[0069] The screened natural compounds were validated in vitro, including cell activity assays, enzyme activity assays, and target affinity assays, to determine their activity and specificity for the target structure.

[0070] Based on in vitro experimental results and combined with the compatibility theory of traditional Chinese medicine prescriptions, the traditional Chinese medicine prescriptions were optimized by adjusting the drug composition, dosage, or adding new drug components to improve their targeting of the target structure and to verify the comprehensive activity of the optimized prescriptions on the target.

[0071] In vitro experimental validation includes:

[0072] Cell viability assays were performed to evaluate the effects of natural compounds on cell proliferation using the MTT or CCK-8 assays.

[0073] Enzyme activity assays use colorimetric or fluorescence methods to determine the inhibitory or activating effects of natural compounds on the activity of target enzymes.

[0074] Target affinity experiments were conducted by determining the binding constant between the natural compound and the target using surface plasmon resonance technology or isothermal titration calorimetry.

[0075] Specifically, in vitro validation is a crucial step in evaluating the biological activity and pharmacological effects of natural compounds, primarily including cell activity assays, enzyme activity assays, and target affinity assays. Cell activity assays use the MTT or CCK-8 assays to detect the effect of natural compounds on cell proliferation. These two methods are based on cellular metabolic activity, reflecting cell number and activity status through color changes, thereby determining the compound's cytotoxicity or proliferative capacity. Enzyme activity assays use colorimetric or fluorescence methods to determine the inhibitory or activating effect of natural compounds on target enzyme activity. The pharmacological activity of the compound is assessed by detecting the amount of enzyme-catalyzed reaction products generated, providing a basis for studying its mechanism of action. Target affinity assays determine the binding constant between the natural compound and the target using surface plasmon resonance technology or isothermal titration calorimetry. These techniques enable real-time, label-free monitoring of intermolecular interactions, accurately measuring binding strength and kinetic parameters, contributing to a deeper understanding of the interaction mechanisms between compounds and targets, and providing important data support for drug screening and optimization.

[0076] In vivo experimental verification includes:

[0077] Construct animal models associated with specific diseases, such as cardiovascular disease models, tumor models, or nervous system disease models;

[0078] The therapeutic effects of the optimized traditional Chinese medicine prescription on animal models were evaluated, including pathological indicators, recovery of physiological functions, and survival rate.

[0079] The safety of the prescription is assessed through toxicological experiments, including acute toxicity, chronic toxicity, and pharmacokinetic studies.

[0080] Specifically, by constructing animal models related to specific diseases, such as cardiovascular diseases, tumors, or nervous system diseases, the pathophysiological processes of human diseases can be simulated, providing a reliable experimental platform for evaluating the efficacy of traditional Chinese medicine (TCM) prescriptions. In these models, researchers can evaluate in detail the therapeutic effects of TCM prescriptions on diseases, including improvements in pathological indicators (such as tumor shrinkage and restoration of vascular endothelial function), restoration of physiological functions (such as improved cardiac function and improved neurobehavioral scores), and changes in animal survival rates, thus objectively reflecting the clinical application potential of TCM prescriptions. Simultaneously, toxicological experiments are also a crucial component of in vivo validation. Acute toxicity experiments assess the potential harm of TCM prescriptions to animals in a short period, while chronic toxicity experiments examine the safety of long-term use. Pharmacokinetic studies help understand the absorption, distribution, metabolism, and excretion processes of TCM components in the body, providing a scientific basis for rational clinical drug use. These comprehensive in vivo experimental validations not only ensure the effectiveness and safety of TCM prescriptions but also lay a solid foundation for their subsequent clinical application and industrial development.

[0081] The optimized traditional Chinese medicine prescriptions were validated in vivo through experiments, including animal model experiments, to evaluate their therapeutic effects and safety for specific diseases.

[0082] The optimized traditional Chinese medicine prescriptions are used in the treatment of specific diseases such as cardiovascular diseases, tumors, and nervous system diseases, including but not limited to prevention, treatment, and adjuvant therapy.

[0083] Specifically, in the optimization process of traditional Chinese medicine (TCM) prescriptions, animal model experiments are used to comprehensively evaluate the therapeutic effects and safety of the optimized TCM prescriptions for specific diseases. By constructing animal models similar to human diseases, such as cardiovascular disease, tumor, or nervous system disease models, researchers can simulate the pathophysiological processes of diseases and observe the therapeutic performance of TCM prescriptions in these models. For example, in cardiovascular disease models, the protective effect of TCM against myocardial ischemia-reperfusion injury, its ability to regulate blood lipid levels, and its effect on improving vascular endothelial function can be evaluated; in tumor models, the inhibitory effect of TCM on tumor growth, its ability to induce tumor cell apoptosis, and its regulatory effect on the body's immune function can be observed; in nervous system disease models, the protective effect of TCM on nerve cell damage, its inhibitory effect on neuroinflammation, and its promoting effect on the recovery of nerve function can be studied. In addition, safety assessment is also an important part of in vivo experiments. Through acute toxicity, chronic toxicity experiments, and pharmacokinetic studies, it is ensured that the TCM prescriptions have no significant toxic side effects on the body at effective doses and have good pharmacokinetic characteristics. The optimized traditional Chinese medicine prescriptions have broad application prospects in the treatment of specific diseases such as cardiovascular diseases, tumors, and nervous system diseases. They can not only be used as the main treatment to directly intervene in the disease process, but also for disease prevention to reduce the risk of disease occurrence, or as an adjunct treatment to enhance the effects of other treatments, reduce treatment side effects, and improve the quality of life of patients.

[0084] Based on the experimental results, the application of traditional Chinese medicine prescriptions in the treatment of specific diseases was determined, and quality control standards and production processes were established.

[0085] The complexes of the screened natural compounds and target structures can be used for target validation, drug design templates, and drug screening targets in drug development. The structural information of the complexes is resolved using high-resolution technology and used to guide the subsequent optimization and development of drugs.

[0086] Specifically, by analyzing the binding of natural compounds to targets, the mechanism of action of targets in disease development can be confirmed, further validating the feasibility and effectiveness of targets and laying the foundation for subsequent drug development. Secondly, the structural information of the complex can serve as a template for drug design. Researchers can design and synthesize new compounds based on the binding mode and interaction details of the complex, optimize their chemical structure, enhance their binding affinity and specificity to the target, and improve drug efficacy. Furthermore, the complex can also serve as a drug screening target, used to screen compounds with similar activities, expanding the compound library for drug development and providing clues for the discovery of novel drugs. The structural information of the complex is usually resolved using high-resolution technology. This detailed information can visually demonstrate the binding details between natural compounds and targets, including binding sites and interaction modes, providing precise guidance for subsequent drug optimization and development, and contributing to the development of safer and more effective drugs.

[0087] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine prescription targeting screening and reusing technology based on natural compounds and target structures, characterized in that, The method comprises the following steps: A traditional Chinese medicine prescription database is established, which contains the composition, efficacy, indications, source and historical application records of traditional Chinese medicine prescriptions; A natural compound database is established, which contains the chemical structure, physicochemical properties, biological activity, source plant or organism, extraction method and known pharmacological effects of natural compounds; A target structure database is established, which contains the three-dimensional structure, biological activity, mechanism of action, disease relevance and known ligand information of the target; Using computer-aided drug design techniques, combined with molecular docking, molecular dynamics simulation and pharmacophore modeling, natural compounds in traditional Chinese medicine prescriptions are screened for targeting, natural compounds with high affinity to target structures are screened out, and their binding sites and modes of action are recorded; The screened natural compounds are verified by in vitro experiments, including cell activity experiments, enzyme activity experiments and target affinity experiments, to determine their activity and specificity for the target structure; The priority score of the compound is calculated and sorted, and the compound is scored based on its biological activity, ADME-T characteristics and other parameters; The priority score of the compound is calculated and sorted based on its biological activity, ADME-T characteristics and other parameters. The candidate compounds with good ADME-T characteristics are used to find the herb collection containing such compounds, and the herb score is calculated and sorted based on the compound priority score, to obtain the herb collection; Based on the obtained herb collection, the related traditional prescriptions are found in reverse. Then, the found prescriptions are scored and sorted according to the herb score to find the candidate prescriptions; The optimized traditional Chinese medicine prescription is verified by in vivo experiments, including animal model experiments, to evaluate its therapeutic effect and safety for specific diseases; Based on the experimental results, the application of the traditional Chinese medicine prescription in treating specific diseases is determined, and the quality control standard and production process are established; According to the in vitro experimental results, the traditional Chinese medicine prescription is optimized by combining with the compatibility theory of traditional Chinese medicine, the drug composition, dosage or new drug ingredients are adjusted to improve the targeting of the target structure, and the comprehensive activity of the optimized prescription for the target is verified.

2. The traditional Chinese medicine prescription targeting screening and reusing technology based on natural compounds and target structures according to claim 1, characterized in that, The prescriptions in the traditional Chinese medicine prescription database are derived from classical Chinese medicine literature and are classified and sorted in combination with modern clinical application cases.

3. The traditional Chinese medicine prescription targeting screening and reusing technology based on natural compounds and target structures according to claim 1, characterized in that, The compounds in the natural compound database include natural products extracted from plants, animals and microorganisms, as well as derivatives obtained by chemical modification, and the structure information of each compound is confirmed by high-resolution mass spectrometry and nuclear magnetic resonance technology.

4. The natural compound and target structure-based traditional Chinese medicine prescription targeting screening and reusing technology according to claim 1, characterized in that, The targets in the target structure database include biological macromolecules such as proteins, nucleic acids and enzymes, and their three-dimensional structures are obtained by X-ray crystallography, nuclear magnetic resonance spectroscopy or cryo-electron microscopy technology, and the biological activity of each target is verified by in vitro experiments and literature review.

5. The natural compound and target structure-based traditional Chinese medicine prescription targeting screening and reusing technology according to claim 1, characterized in that, The computer-aided drug design techniques include: Molecular docking software is used to preliminarily screen natural compounds and target structures, calculate binding energy and predict binding sites; The stability of the complex of the screened natural compound and the target point is evaluated by molecular dynamics simulation, and the simulation time is not less than 100 ns; The active groups of the natural compounds are analyzed based on the pharmacophore model, and the screening conditions are optimized to improve the screening efficiency and accuracy. According to the drug use, the ADMET is screened, such as transdermal absorption potential and skin irritation for external drugs, and oral absorption rate for oral drugs.

6. The natural compound and target structure-based traditional Chinese medicine prescription targeting screening and reusing technology according to claim 1, characterized in that, The in vitro experimental verification includes: Cell activity experiment: the influence of natural compounds on cell proliferation is evaluated by MTT method or CCK-8 method; Enzyme activity experiment: the inhibition or activation of natural compounds on target enzyme activity is determined by colorimetric method or fluorescence method; Target affinity experiment: the binding constant of natural compounds and target is determined by surface plasmon resonance technology or isothermal titration calorimetry.

7. The natural compound and target structure-based traditional Chinese medicine prescription targeting screening and reusing technology according to claim 1, characterized in that, The in vivo experimental verification includes: Construction of animal models related to specific diseases, such as cardiovascular disease model, tumor model or nervous system disease model; Evaluation of the therapeutic effect of the optimized traditional Chinese medicine prescription on animal models, including pathological indicators, physiological function recovery and survival rate, etc. Safety evaluation of the prescription through toxicology experiment, including acute toxicity, chronic toxicity and pharmacokinetic study.

8. The traditional Chinese medicine prescription targeting screening and reusing technology based on natural compounds and target structures according to claim 1, characterized in that, The application of the optimized traditional Chinese medicine prescription in the treatment of specific diseases such as cardiovascular disease, tumor and nervous system disease, including but not limited to prevention, treatment and adjuvant therapy.

9. The natural compound and target structure-based traditional Chinese medicine prescription targeting screening and reusing technology according to claim 1, characterized in that, The complex of the screened natural compound and the target structure can be used for target verification, drug design template and drug screening target in drug research and development, and the structural information of the complex is analyzed by high-resolution technology and used to guide the optimization and development of subsequent drugs.

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