Glycyrrhizic acid antiviral analysis method and system based on molecular virtual docking

Abstract

The invention relates to the field of medicines, and discloses a glycyrrhizic acid antiviral analysis method based on molecular virtual docking, and the method comprises the following steps: obtaining glycyrrhizic acid and a key virus protein corresponding to the glycyrrhizic acid, carrying out docking pretreatment on the key virus protein and the glycyrrhizic acid, carrying out docking treatment on the key virus protein and the glycyrrhizic acid, and carrying out molecular virtual docking on the key virus protein and the glycyrrhizic acid. Analyzing the interaction type of the key virus protein and the glycyrrhizic acid according to the docking processing result, obtaining the binding free energy and affinity of the key virus protein and the glycyrrhizic acid so as to determine the target binding mode of the key virus protein and the glycyrrhizic acid, and analyzing the antiviral effect of the glycyrrhizic acid according to the target binding mode. According to the method, the drug molecules with potential activity can be accurately screened out, and the accuracy of an antiviral analysis result is improved.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a glycyrrhizic acid antiviral analysis method and system based on molecular virtual docking. Background Art

[0002] Glycyrrhizic acid antiviral analysis refers to the process of studying the role and mechanism of glycyrrhizic acid as a natural compound in antiviral treatment. Glycyrrhizic acid is a triterpenoid saponin extracted from the root of licorice. It has multiple biological activities, including anti-inflammatory, antiviral and immunomodulatory effects. With the increasing prominence of global public health security issues, it is particularly important to find effective antiviral drugs. Glycyrrhizic acid has become a key object of antiviral drug research due to its unique antiviral mechanism and significant pharmacological activity.

[0003] In the prior art, the antiviral analysis of glycyrrhizic acid mainly adopts the cell culture method. This method evaluates the antiviral effect of glycyrrhizic acid by culturing glycyrrhizic acid with virus-infected cells and observing the changes in indicators such as viral replication, cytopathic effect and cell survival rate. Although this method has high reliability, due to the relatively long entire experimental cycle, it may cause changes in cell status and affect the accuracy of the antiviral analysis results. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a glycyrrhizic acid antiviral analysis method and system based on molecular virtual docking, which can ensure the security of data sharing and improve the trust between data providers and data requesters.

[0005] In a first aspect, the present invention provides a glycyrrhizic acid antiviral analysis method based on molecular virtual docking, comprising: Obtaining glycyrrhizic acid to be analyzed and its corresponding target virus, identifying the key viral protein of the target virus, and obtaining the three-dimensional structure of the key viral protein, performing conformational optimization on the three-dimensional structure, and obtaining the target viral protein molecule; Identify the chemical components of the glycyrrhizic acid, analyze the antiviral properties of the glycyrrhizic acid based on the chemical components, extract the key chemical components of the glycyrrhizic acid based on the antiviral properties, query the three-dimensional chemical structure of the key chemical components, and perform docking pre-processing on the three-dimensional chemical structure based on the target protein molecule to obtain the target glycyrrhizic acid molecule; Analyze the functional factors of the key viral protein, wherein the functional factors include virological functional factors and pharmacological functional factors, determine the molecular docking region of the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, and perform docking processing on the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region to obtain a docking result; According to the docking result, the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule is identified; based on the binding mode, the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule is analyzed; according to the interaction type, the binding free energy of the target glycyrrhizic acid molecule and the target viral protein molecule is calculated; based on the binding free energy, the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule is analyzed; In combination with the interaction type, the binding free energy and the affinity, the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule is determined, and based on the target binding mode, the antiviral effect of the glycyrrhizic acid is analyzed.

[0006] In a possible implementation of the first aspect, performing conformational optimization on the three-dimensional structure to obtain a target viral protein molecule includes: identifying constituent molecules of the three-dimensional structure; Extracting water molecules from the constituent molecules and removing the water molecules to obtain a dehydrated protein structure; hydrogenating the dehydrated protein structure to obtain a hydrogenated protein structure; calculating a charge factor of the hydrogenated protein structure; analyzing the atomic types of the hydrogenated protein structure based on the charge factors; According to the atom type, the target viral protein molecule is obtained.

[0007] In a possible implementation of the first aspect, extracting the key chemical components of glycyrrhizic acid according to the antiviral properties includes: Query the chemical composition of the glycyrrhizic acid; According to the antiviral property, setting an activity evaluation index of the chemical component; Calculating the virus inhibition effect ratio of the chemical component according to the activity evaluation index; Based on the virus inhibition effect ratio, the key chemical components of the glycyrrhizic acid are extracted.

[0008] In a possible implementation of the first aspect, analyzing the functional factors of the key viral protein includes: Identify the viral species of the key viral protein; analyzing the viral replication cycle of the virus species; Based on the viral replication cycle, identifying the pathogenic mechanism of the key viral protein; Determine the virological functional factors of the key viral proteins in combination with the viral replication cycle and the pathogenic mechanism; Identifying the influencing factors of the pathogenic mechanism and analyzing the viral inhibitory effect of the key viral protein based on the influencing factors; Based on the virus inhibition effect, determining the pharmacological functional factors of the key viral protein; The functional factors of the key viral proteins are analyzed by combining the virological functional factors and the pharmacological functional factors.

[0009] In a possible implementation of the first aspect, the docking process of the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region includes: Based on the molecular docking region, determining the docking site between the target protein molecule and the target glycyrrhizic acid molecule; Setting the docking file format of the target protein molecule and the target glycyrrhizic acid molecule; According to the docking site, setting a docking box between the target protein molecule and the target glycyrrhizic acid molecule; Based on the docking box, defining the docking parameters of the target protein molecule and the target glycyrrhizic acid molecule; In combination with the docking file format and the docking parameters, the target protein molecule and the target glycyrrhizic acid molecule are docked to obtain a docking result.

[0010] In a second aspect, the present invention provides a glycyrrhizic acid antiviral analysis system based on molecular virtual docking, characterized in that the system comprises: A virus protein processing module, used to obtain the glycyrrhizic acid to be analyzed and its corresponding target virus, identify the key virus protein of the target virus, obtain the three-dimensional structure of the key virus protein, perform conformation optimization processing on the three-dimensional structure, and obtain the target virus protein molecule; A glycyrrhizic acid processing module, used to identify the chemical components of the glycyrrhizic acid, analyze the antiviral properties of the glycyrrhizic acid based on the chemical components, extract the key chemical components of the glycyrrhizic acid based on the antiviral properties, query the three-dimensional chemical structure of the key chemical components, and perform docking pre-processing on the three-dimensional chemical structure based on the target protein molecule to obtain the target glycyrrhizic acid molecule; A molecular docking processing module, used to analyze the functional factors of the key viral protein, wherein the functional factors include virological functional factors and pharmacological functional factors, and determine the molecular docking region of the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, and perform docking processing on the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region to obtain a docking result; A binding mode analysis module, for identifying the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule according to the docking result, analyzing the type of interaction between the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding mode, calculating the binding free energy of the target glycyrrhizic acid molecule and the target viral protein molecule according to the interaction type, and analyzing the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding free energy; The antiviral result analysis module is used to determine the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule based on the interaction type, the binding free energy and the affinity, and analyze the antiviral effect of the glycyrrhizic acid based on the target binding mode.

[0011] Compared with the prior art, the technical principle and beneficial effects of this solution are: The embodiment of the present invention can provide a clear direction for subsequent experiments and analyses by obtaining the glycyrrhizic acid to be analyzed and its corresponding target virus. By analyzing the functional factors of the key viral protein, it can help understand the survival and transmission mode of the virus in the host, and how to prevent the replication and infection of the virus by inhibiting these functional factors. Furthermore, the embodiment of the present invention can find the best site for the binding of the glycyrrhizic acid molecule to the viral protein by determining the molecular docking region of the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, thereby screening out the glycyrrhizic acid molecules that may have an inhibitory effect on the virus, and docking the target protein molecule and the target glycyrrhizic acid molecule to obtain the docking result, which can help predict the binding mode of the glycyrrhizic acid molecule to the viral protein and analyze the interaction between the glycyrrhizic acid molecule and the viral protein. At the same time, the docking result can guide medicinal chemists to optimize the structure of the glycyrrhizic acid molecule to improve its binding affinity and selectivity with the viral protein, thereby enhancing its antiviral activity. The embodiment of the present invention can understand how the drug molecule interacts with the target protein by identifying the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule according to the docking result, thereby revealing the mechanism of action of the drug. The present invention discloses a method for analyzing the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule, which can help understand how molecules interact with each other and the nature and strength of these interactions. By analyzing the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding free energy, detailed information on how the virus interacts with the host cell can be provided, which helps predict the infectivity and mutation potential of the virus and improves the accuracy of glycyrrhizic acid in antiviral analysis. The embodiment of the present invention determines the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule by combining the interaction type, the binding free energy and the affinity. The target binding mode of the molecule can be used to screen glycyrrhizic acid derivatives or compounds of similar structures with antiviral potential, thereby helping to calculate the glycyrrhizic acid concentration required to achieve the therapeutic effect, improving the safety and accuracy of glycyrrhizic acid antiviral analysis, and by analyzing the antiviral effect of the glycyrrhizic acid based on the target binding mode, we can gain an in-depth understanding of how glycyrrhizic acid interacts with viral proteins, thereby blocking the replication cycle of the virus or destroying its structural integrity. By optimizing the structure of the glycyrrhizic acid molecule, its binding affinity with viral proteins can be enhanced, thereby improving the antiviral effect, and at the same time being able to predict the risk of viral resistance to glycyrrhizic acid. Therefore, the glycyrrhizic acid antiviral analysis method based on molecular virtual docking proposed in the embodiment of the present invention can accurately screen out drug molecules with potential activity and improve the accuracy of the antiviral analysis results. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0013] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0014] Figure 1 A schematic diagram of a process for analyzing glycyrrhizic acid antiviral activity based on molecular virtual docking provided by one embodiment of the present invention; Figure 2 A schematic diagram of a module of a glycyrrhizic acid antiviral analysis system based on molecular virtual docking provided by an embodiment of the present invention. DETAILED DESCRIPTION

[0015] It should be understood that the specific embodiments described herein are only used to explain the present invention, and are not used to limit the present invention.

[0016] The embodiment of the present invention provides a glycyrrhizic acid antiviral analysis method based on molecular virtual docking, and the execution subject of the glycyrrhizic acid antiviral analysis method based on molecular virtual docking includes but is not limited to at least one of the electronic devices such as a server and a terminal that can be configured to execute the method provided by the embodiment of the present invention. In other words, the glycyrrhizic acid antiviral analysis method based on molecular virtual docking can be executed by software or hardware installed on a terminal device or a server device, and the software can be a blockchain platform. The server includes but is not limited to: a single server, a server cluster, a cloud server or a cloud server cluster, etc. The server can be an independent server, or it can be a cloud server that provides cloud services, cloud databases, cloud computing, cloud functions, cloud storage, network services, cloud communications, middleware services, domain name services, security services, content delivery networks (Content Delivery Network, CDN), and basic cloud computing services such as big data and artificial intelligence platforms.

[0017] See also Figure 1 FIG. 1 is a flow chart of a method for analyzing glycyrrhizic acid antiviral activity based on molecular virtual docking according to an embodiment of the present invention. Figure 1 The molecular virtual docking-based glycyrrhizic acid antiviral analysis method described in the paper includes: S1. Obtain glycyrrhizic acid to be analyzed and its corresponding target virus, identify the key viral protein of the target virus, obtain the three-dimensional structure of the key viral protein, perform conformational optimization on the three-dimensional structure, and obtain the target viral protein molecule.

[0018] The embodiment of the present invention can provide a clear direction for subsequent experiments and analyses by obtaining glycyrrhizic acid to be analyzed and its corresponding target virus, wherein the glycyrrhizic acid refers to a natural compound extracted from the root of the licorice plant, and the target virus refers to a virus used to evaluate the antiviral effect of glycyrrhizic acid.

[0019] Optionally, the glycyrrhizic acid to be analyzed and its corresponding target virus can be obtained through a laboratory.

[0020] Furthermore, the embodiments of the present invention can determine important targets in drug development by identifying the key viral proteins of the target virus and obtaining the three-dimensional structure of the key viral proteins. The three-dimensional structure provides detailed atomic-level information. Through the three-dimensional structure, molecular docking simulation can be performed to predict the interaction between drug molecules and key viral proteins. The key viral proteins refer to proteins that play an important role in the life cycle of the virus. These proteins are usually key components for the survival, replication and spread of the virus. The three-dimensional structure refers to the three-dimensional form of the protein in space, including the spatial arrangement of amino acid residues, secondary structures (such as α-helix, β-fold) and the overall conformation of the protein.

[0021] Optionally, the identification of the key viral protein of the target virus can be obtained by comparing the gene sequence of the target virus through bioinformatics tools, such as BLAST tools, and the three-dimensional structure of the key viral protein can be obtained using X-ray diffraction technology.

[0022] The embodiment of the present invention obtains the target viral protein molecule by performing conformational optimization on the three-dimensional structure, thereby removing the unreasonable geometric conformation in the structure, making the structure closer to the real physical state, and improving the shape and size of the drug binding pocket through conformational optimization to make it more suitable for the binding of drug molecules. The target viral protein molecule refers to a specific viral protein molecule obtained after a series of treatments and optimizations.

[0023] As an embodiment of the present invention, the conformational optimization processing of the three-dimensional structure to obtain the target viral protein molecule includes: identifying the constituent molecules of the three-dimensional structure; extracting the water molecules of the constituent molecules and removing the water molecules to obtain a dehydrated protein structure; hydrogenating the dehydrated protein structure to obtain a hydrogenated protein structure; calculating the charge factor of the hydrogenated protein structure; analyzing the atomic type of the hydrogenated protein structure based on the charge factor; and obtaining the target viral protein molecule according to the atomic type.

[0024] Among them, the constituent molecules refer to all molecules that constitute the three-dimensional structure of the protein, including the amino acid chain, cofactors, metal ions, water molecules, etc. of the protein itself; the water molecules refer to molecules composed of two hydrogen atoms (H) and one oxygen atom (O) existing in the three-dimensional structure of the protein; the dehydrated protein structure refers to a protein structure that does not contain water molecules; the hydrogenated protein structure refers to a protein structure generated after adding all the missing hydrogen atoms to the protein structure; the charge factor refers to the charge value of each atom in the protein structure; and the atom type refers to the chemical type of each atom, such as hydrophobicity and polarity.

[0025] Optionally, the removal of water molecules can be achieved using the PyMOL tool, the hydrogenation of the dehydrated protein structure can be obtained using the H++ tool, the charge factor calculation of the hydrogenated protein structure based on the hydrogenated protein structure can be achieved using the Propka tool, and the atomic type analysis of the hydrogenated protein structure based on the charge factor can be obtained by assigning atomic types to each atom through the ACEDRG tool.

[0026] S2. Identify the chemical components of the glycyrrhizic acid, analyze the antiviral properties of the glycyrrhizic acid based on the chemical components, extract the key chemical components of the glycyrrhizic acid based on the antiviral properties, query the three-dimensional chemical structure of the key chemical components, and perform docking pre-processing on the three-dimensional chemical structure based on the target protein molecule to obtain the target glycyrrhizic acid molecule.

[0027] The embodiments of the present invention can better understand the application of glycyrrhizic acid in antiviral treatment by identifying the chemical components of glycyrrhizic acid, wherein the chemical components refer to the specific molecules and chemical structures constituting glycyrrhizic acid, such as glycyrrhetinic acid and glucuronic acid.

[0028] Optionally, the chemical composition identification of glycyrrhizic acid can be achieved using high performance liquid chromatography analysis technology.

[0029] Furthermore, the embodiments of the present invention analyze the antiviral properties of the glycyrrhizic acid based on the chemical composition, thereby understanding the antiviral mechanism of action of glycyrrhizic acid and improving the accuracy of the glycyrrhizic acid antiviral experiment. The antiviral properties refer to the viral inhibition properties of glycyrrhizic acid on certain viruses.

[0030] Optionally, the antiviral property analysis of the glycyrrhizic acid based on the chemical composition can be obtained through cell experiments.

[0031] The embodiment of the present invention can study the biological activity and mechanism of action of the key chemical components by extracting the key chemical components of glycyrrhizic acid based on the antiviral properties, and provide important theoretical support and practical guidance for drug research and development. The key chemical components refer to the most active or functional chemical components in glycyrrhizic acid, such as glycyrrhetinic acid.

[0032] As an embodiment of the present invention, extracting the key chemical components of the glycyrrhizic acid based on the antiviral properties includes: querying the chemical components of the glycyrrhizic acid; setting an activity evaluation index of the chemical components based on the antiviral properties; calculating the virus inhibition effect ratio of the chemical components based on the activity evaluation index; and extracting the key chemical components of the glycyrrhizic acid based on the virus inhibition effect ratio.

[0033] Among them, the activity evaluation index refers to the specific standard used to evaluate the antiviral effect of glycyrrhizic acid and its chemical components, and the virus inhibition effect ratio refers to the antiviral effect of glycyrrhizic acid and its chemical components calculated by the activity evaluation index.

[0034] Optionally, according to the antiviral property, the activity evaluation index setting of the chemical component can be achieved by utilizing the antiviral effect, such as the virus replication level and cell survival rate.

[0035] Furthermore, the embodiments of the present invention can perform molecular docking simulation with viral proteins and predict the interaction between drug molecules and key viral proteins by querying the three-dimensional chemical structure of the key chemical component, wherein the three-dimensional chemical structure refers to the three-dimensional form of the key chemical component of glycyrrhizic acid in space.

[0036] Optionally, the three-dimensional chemical structure query of the key chemical component can be achieved by using electron diffraction.

[0037] The embodiment of the present invention obtains a target glycyrrhizic acid molecule by performing docking pre-processing on the three-dimensional chemical structure based on the target protein molecule, thereby ensuring the accuracy and reliability of the glycyrrhizic acid molecular structure, thereby improving the accuracy of molecular docking. The target glycyrrhizic acid molecule refers to the glycyrrhizic acid molecular structure after molecular docking pre-processing.

[0038] Optionally, the pre-docking processing of the three-dimensional chemical structure based on the target protein molecule can be obtained by an operation method of the target viral protein molecule.

[0039] S3. Analyze the functional factors of the key viral protein, wherein the functional factors include virological functional factors and pharmacological functional factors, determine the molecular docking region between the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, and perform docking processing on the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region to obtain a docking result.

[0040] The embodiments of the present invention can help understand how the virus survives and spreads in the host, and how to prevent viral replication and infection by inhibiting these functional factors by analyzing the functional factors of the key viral proteins. The functional factors refer to the various key roles played by viral proteins in the viral life cycle, including virological functions and pharmacological functions.

[0041] As an embodiment of the present invention, the analysis of the functional factors of the key viral protein includes: identifying the virus type of the key viral protein; analyzing the viral replication cycle of the virus type; based on the viral replication cycle, identifying the pathogenic mechanism of the key viral protein; combining the viral replication cycle and the pathogenic mechanism, determining the virological functional factors of the key viral protein; identifying the influencing factors of the pathogenic mechanism, and analyzing the viral inhibitory effect of the key viral protein based on the influencing factors; based on the viral inhibitory effect, determining the pharmacological functional factors of the key viral protein; combining the virological functional factors and the pharmacological functional factors, analyzing the functional factors of the key viral protein.

[0042] Among them, the virus type refers to the virus type classified according to the different characteristics of the virus, the virus replication cycle refers to the whole process from the virus entering the host cell to the production of new virus particles, the pathogenic mechanism refers to the process mechanism of how viral proteins cause the occurrence and development of the disease, the virological functional factor refers to the specific function of viral proteins in the virus life cycle, the influencing factors refer to various factors that affect the viral pathogenic mechanism, such as host cell status and immune response, etc., the viral inhibitory factor refers to the inhibitory effect on the virus through specific methods or drugs, and the pharmacological functional factor refers to the key factor of interaction with drugs when viral proteins are used as drug targets.

[0043] Optionally, the virus species identification of the key viral protein can be obtained through a virology database, such as the NCBI database, and the virus replication cycle analysis of the virus species can be achieved using the UniProt database. The identification of the pathogenic mechanism of the key viral protein based on the viral replication cycle can be obtained through a cell experimental method, and the analysis of the virus inhibition effect of the key viral protein based on the influencing factors can be achieved by simulating the binding of drugs and viral proteins using molecular docking software, such as AutoDock software.

[0044] Furthermore, the embodiments of the present invention can find the optimal site for binding of the glycyrrhizic acid molecule to the viral protein by determining the molecular docking region between the target protein molecule and the target glycyrrhizic acid molecule based on the functional factor, thereby screening out glycyrrhizic acid molecules that may have an inhibitory effect on the virus. The molecular docking region refers to the region on the target protein that may interact with the target glycyrrhizic acid molecule, also known as the active site or receptor binding site.

[0045] Optionally, according to the functional factors, the molecular docking region between the target protein molecule and the target glycyrrhizic acid molecule can be determined by functional site mapping, such as mapping the functional information of the viral protein to its three-dimensional structure, identifying the key amino acid residues or regions directly related to the specific function, and obtaining the hotspot area of ​​the molecular docking.

[0046] The embodiment of the present invention performs docking processing on the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region to obtain a docking result, which can help predict the binding mode of the glycyrrhizic acid molecule with the viral protein and analyze the interaction between the glycyrrhizic acid molecule and the viral protein. At the same time, the docking result can guide medicinal chemists to perform structural optimization of the glycyrrhizic acid molecule to improve its binding affinity and selectivity with the viral protein, thereby enhancing its antiviral activity. The docking result refers to a series of data generated by the target protein molecule and the target glycyrrhizic acid molecule during the molecular docking process.

[0047] As an embodiment of the present invention, the target protein molecule and the target glycyrrhizic acid molecule are docked based on the molecular docking region, including: determining the docking site of the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region; setting the docking file format of the target protein molecule and the target glycyrrhizic acid molecule; setting the docking box of the target protein molecule and the target glycyrrhizic acid molecule according to the docking site; defining the docking parameters of the target protein molecule and the target glycyrrhizic acid molecule based on the docking box; and docking the target protein molecule and the target glycyrrhizic acid molecule in combination with the docking file format and the docking parameters to obtain a docking result.

[0048] Among them, the docking site refers to the position where a stable bond is most likely to be formed between the target protein molecule and the target glycyrrhizic acid molecule, the docking box refers to a three-dimensional space region defined in the molecular docking process, the docking file format refers to the file format used for molecular docking, common ones include PDB, SDF, MOL, etc., and the docking parameters refer to various parameters that need to be set in the molecular docking process, including search algorithms, evaluation functions, etc.

[0049] Optionally, the determination of the docking site of the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region can be achieved using an online docking platform, such as a ZDOCK platform, the docking file format setting of the target protein molecule and the target glycyrrhizic acid molecule can be obtained through a format conversion tool, such as an OpenBabel tool, and the docking box setting of the target protein molecule and the target glycyrrhizic acid molecule according to the docking site can be achieved using a docking box setting function built into a molecular docking software.

[0050] S4. According to the docking result, the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule is identified; based on the binding mode, the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule is analyzed; according to the interaction type, the binding free energy between the target glycyrrhizic acid molecule and the target viral protein molecule is calculated; based on the binding free energy, the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule is analyzed.

[0051] The embodiment of the present invention can understand how the drug molecule interacts with the target protein by identifying the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule according to the docking result, thereby revealing the mechanism of action of the drug. The binding mode refers to the binding state of a specific spatial conformation and interaction relationship formed between two or more molecules (such as ligands and receptors, drugs and targets, etc.) during the process of molecular recognition and interaction.

[0052] As an embodiment of the present invention, identifying the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule according to the docking result includes: identifying the active site of the target viral protein molecule according to the docking result; locating the target glycyrrhizic acid molecule in the search space of the target viral protein molecule based on the active site; identifying the multi-attribute conformation of the target glycyrrhizic acid molecule according to the search space; analyzing the potential interaction between the multi-attribute conformation and the target viral protein molecule; and identifying the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule in combination with the multi-attribute conformation and the potential interaction.

[0053] Among them, the active site refers to the key area in the protein that specifically binds to the glycyrrhizic acid molecule, the search space refers to the collection of various positions and postures that the glycyrrhizic acid molecule may take around the active site, the multi-attribute conformation refers to the various conformations that the glycyrrhizic acid molecule may take under different conditions, including geometric conformation, charge distribution, etc., and the potential interaction refers to the physical and chemical interactions that may occur between the glycyrrhizic acid molecule and the protein, such as hydrogen bonds, van der Waals forces, hydrophobic effects, etc.

[0054] Optionally, according to the docking result, the active site identification of the target viral protein molecule can be calculated by molecular docking software, such as Schrodinger's Maestro software. Based on the active site, the positioning of the target glycyrrhizic acid molecule in the search space of the target viral protein molecule can be determined by the search algorithm in the molecular docking software, such as a genetic algorithm. According to the search space, the multi-attribute conformation identification of the target glycyrrhizic acid molecule can be obtained by a conceptual thinking algorithm. The potential interaction analysis of the multi-attribute conformation and the target viral protein molecule can be achieved by force field calculation in molecular simulation to evaluate the interaction energy under each conformation.

[0055] Furthermore, the embodiments of the present invention can help understand how molecules interact with each other and the nature and strength of these interactions by analyzing the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding mode. The interaction type refers to different types of physicochemical interactions that may occur between molecules, such as hydrophobic interactions.

[0056] Optionally, the analysis of the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding mode can be achieved using a PLIP tool.

[0057] The embodiment of the present invention can predict the potential efficacy of glycyrrhizic acid and reveal the molecular mechanism of the antiviral effect of glycyrrhizic acid by calculating the binding free energy between the target glycyrrhizic acid molecule and the target viral protein molecule according to the interaction type. The binding free energy refers to a quantitative indicator for measuring the binding strength between the glycyrrhizic acid molecule and the viral protein molecule.

[0058] In an optional embodiment of the present invention, according to the interaction type, the binding free energy between the target glycyrrhizic acid molecule and the target viral protein molecule is calculated using the following formula: in, represents the binding free energy between the target glycyrrhizic acid molecule and the target viral protein molecule, represents the molecular internal energy of the target glycyrrhizic acid molecule and the target viral protein molecule, represents the electrostatic interaction energy between the target glycyrrhizic acid molecule and the charged particles in the target viral protein molecule, represents the van der Waals energy between the target glycyrrhizic acid molecule and the target viral protein molecule, It indicates the change of interaction energy between target glycyrrhizic acid molecule and target viral protein molecule in solvent due to charge distribution. Represents the change in nonpolar solvation energy between the target glycyrrhizic acid molecule and the target viral protein molecule.

[0059] Furthermore, the embodiments of the present invention can provide detailed information on how the virus interacts with host cells by analyzing the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding free energy, help predict the infectivity and mutation potential of the virus, and improve the accuracy of glycyrrhizic acid in antiviral analysis. The affinity refers to the strength of the interaction between the viral protein molecule and the glycyrrhizic acid molecule.

[0060] As an embodiment of the present invention, the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule is analyzed based on the binding free energy, including: based on the binding free energy, analyzing the interaction change trend between the target glycyrrhizic acid molecule and the target viral protein molecule; according to the interaction change trend, identifying the dissociation tendency of the target glycyrrhizic acid molecule and the target viral protein molecule; based on the binding free energy, calculating the dissociation constant of the dissociation tendency; analyzing the changing relationship between the dissociation constant and the binding free energy; according to the changing relationship, analyzing the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule.

[0061] Among them, the interaction change trend refers to the energy change pattern of the interaction between viral protein molecules and glycyrrhizic acid molecules, the dissociation tendency refers to the tendency of the intermolecular complex to decompose back into its respective components, the dissociation constant refers to the parameter of the equilibrium state of the dissociation reaction between glycyrrhizic acid molecules and viral protein molecules, and the change relationship refers to the way two or more variables interact and influence each other.

[0062] Optionally, the analysis of the interaction change trend between the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding free energy can be obtained through an isothermal titration calorimetry (ITC) system, and the identification of the dissociation tendency between the target glycyrrhizic acid molecule and the target viral protein molecule based on the interaction change trend can be achieved using a molecular dynamics simulation tool, such as a GROMACS tool.

[0063] In an optional embodiment of the present invention, based on the binding free energy, the dissociation constant of the dissociation tendency is calculated using the following formula: Where K represents the dissociation constant of the dissociation tendency, represents binding free energy, R represents the gas constant when the dissociation tendency occurs, T represents the absolute temperature when the dissociation tendency occurs, and e represents the base of the exponential relationship between binding free energy and dissociation constant.

[0064] S5. Determine the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule based on the interaction type, the binding free energy and the affinity, and analyze the antiviral effect of the glycyrrhizic acid based on the target binding mode.

[0065] The embodiment of the present invention determines the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule by combining the interaction type, the binding free energy and the affinity, which can be used to screen glycyrrhizic acid derivatives or compounds of similar structures with antiviral potential, thereby helping to calculate the glycyrrhizic acid concentration required to achieve a therapeutic effect and improving the safety and accuracy of glycyrrhizic acid antiviral analysis. The target binding mode refers to the most stable and lowest energy binding state between the ligand and the receptor molecule during the molecular docking process.

[0066] As an embodiment of the present invention, the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule is determined by combining the interaction type, the binding free energy and the affinity, including: collecting a set of binding modes of the target glycyrrhizic acid molecule and the target viral protein molecule in combination with the interaction type, the binding free energy and the affinity; extracting the interaction parameters of the target glycyrrhizic acid molecule and the target viral protein molecule based on the interaction type; analyzing the contribution of the interaction parameters to the binding free energy and the affinity; setting a scoring mechanism for the binding mode set according to the contribution; and determining the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule based on the scoring mechanism.

[0067] Among them, the binding mode set refers to the possible binding mode set between viral protein molecules and glycyrrhizic acid molecules, the interaction parameters refer to specific numerical values ​​that describe the interaction between molecules, such as hydrogen bond strength, van der Waals force, electrostatic interaction energy, etc., the contribution refers to the degree of optimization of different interaction parameters on binding free energy and affinity, and the scoring mechanism refers to a standard system for evaluating and selecting the best binding mode.

[0068] Optionally, based on the interaction type, the interaction parameter extraction between the target glycyrrhizic acid molecule and the target viral protein molecule can be obtained through an interaction report generated by molecular docking software, and according to the contribution, the scoring mechanism setting of the binding mode set can be implemented using particle swarm optimization, and the contribution analysis of the interaction parameters to the binding free energy and the affinity can be obtained through residue contribution analysis.

[0069] Furthermore, the embodiments of the present invention analyze the antiviral effect of the glycyrrhizic acid based on the target binding mode, and can deeply understand how glycyrrhizic acid interacts with viral proteins, thereby blocking the viral replication cycle or destroying its structural integrity. By optimizing the structure of the glycyrrhizic acid molecule, its binding affinity with the viral protein can be enhanced, thereby improving the antiviral effect, and at the same time, it can predict the risk of viral resistance to glycyrrhizic acid. The antiviral effect refers to the inhibitory effect of glycyrrhizic acid on viruses in vivo or in vitro environments.

[0070] As an embodiment of the present invention, the analysis of the antiviral effect of the glycyrrhizic acid based on the target binding mode includes: extracting the viral protein bound to the glycyrrhizic acid based on the target binding mode; identifying the key binding site between the viral protein bound to the glycyrrhizic acid; analyzing the binding conformation of the glycyrrhizic acid at the key binding site; based on the binding conformation, analyzing the key interaction between the glycyrrhizic acid and the viral protein bound to the glycyrrhizic acid; setting the viral inhibition pathway of the glycyrrhizic acid according to the target binding mode and the key interaction; based on the viral inhibition pathway, identifying the cell receptor binding site of the viral protein bound to the glycyrrhizic acid; analyzing the interference effect of the glycyrrhizic acid on the cell receptor binding site; and analyzing the antiviral effect of the glycyrrhizic acid according to the interference effect.

[0071] Among them, the binding viral protein refers to the viral surface protein or key enzyme that glycyrrhizic acid can bind to, the key binding site refers to the most important binding area between glycyrrhizic acid and viral protein, the binding conformation refers to the specific spatial structure and orientation of glycyrrhizic acid at the key binding site, the key interaction refers to the most important physical and chemical interaction between glycyrrhizic acid and viral protein, the viral inhibition pathway refers to the specific mechanism by which glycyrrhizic acid prevents the virus from entering the cell or inhibits viral replication by binding to viral protein, the cell receptor binding site refers to the key site where the viral surface protein binds to the host cell receptor, and the interference effect refers to the degree of interference of glycyrrhizic acid on the binding of the virus to the host cell receptor.

[0072] Optionally, the identification of the key binding site between the viral protein and the glycyrrhizic acid can be obtained by site-directed mutagenesis experiments, the binding conformation analysis of the glycyrrhizic acid at the key binding site can be achieved using nuclear magnetic resonance experiments, the setting of the viral inhibition pathway of the glycyrrhizic acid based on the target binding mode and the key interaction can be obtained by combining molecular simulation and experimental data, the identification of the cell receptor binding site that binds the viral protein based on the viral inhibition pathway can be achieved using X-ray crystallography, and the analysis of the interference effect of the glycyrrhizic acid on the cell receptor binding site can be obtained through in vitro cell culture experiments.

[0073] It can be seen that the embodiments of the present invention can provide a clear direction for subsequent experiments and analyses by obtaining the glycyrrhizic acid to be analyzed and its corresponding target virus. By analyzing the functional factors of the key viral proteins, it can help understand the survival and transmission mode of the virus in the host, and how to prevent the replication and infection of the virus by inhibiting these functional factors. Furthermore, the embodiments of the present invention can find the best site for the binding of glycyrrhizic acid molecules to viral proteins by determining the molecular docking region of the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, thereby screening out glycyrrhizic acid molecules that may have an inhibitory effect on the virus, and docking the target protein molecule and the target glycyrrhizic acid molecule to obtain docking results, which can help predict the binding mode of glycyrrhizic acid molecules to viral proteins and analyze the interaction between glycyrrhizic acid molecules and viral proteins. At the same time, the docking results can guide medicinal chemists to optimize the structure of glycyrrhizic acid molecules to improve their binding affinity and selectivity with viral proteins, thereby enhancing their antiviral activity. The embodiments of the present invention can understand how drug molecules interact with target proteins by identifying the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule according to the docking results, thereby revealing the mechanism of action of the drug. The binding mode and the analysis of the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule can help understand how molecules interact with each other and the nature and strength of these interactions. By analyzing the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding free energy, detailed information on how the virus interacts with the host cell can be provided, which helps predict the infectivity and mutation potential of the virus and improves the accuracy of glycyrrhizic acid in antiviral analysis. The embodiment of the present invention determines the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule by combining the interaction type, the binding free energy and the affinity. The target binding mode of the white molecule can be used to screen glycyrrhizic acid derivatives or compounds of similar structures with antiviral potential, thereby helping to calculate the glycyrrhizic acid concentration required to achieve the therapeutic effect, and improving the safety and accuracy of glycyrrhizic acid antiviral analysis. By analyzing the antiviral effect of the glycyrrhizic acid based on the target binding mode, we can gain an in-depth understanding of how glycyrrhizic acid interacts with viral proteins, thereby blocking the replication cycle of the virus or destroying its structural integrity. By optimizing the structure of the glycyrrhizic acid molecule, its binding affinity with viral proteins can be enhanced, thereby improving the antiviral effect, and at the same time, it can predict the risk of viral resistance to glycyrrhizic acid. Therefore, the glycyrrhizic acid antiviral analysis method based on molecular virtual docking proposed in the embodiment of the present invention can accurately screen out drug molecules with potential activity and improve the accuracy of the antiviral analysis results.

[0074] like Figure 2 Shown is a system functional module diagram of glycyrrhizic acid antiviral analysis based on molecular virtual docking of the present invention.

[0075] The glycyrrhizic acid antiviral analysis system 200 based on molecular virtual docking of the present invention can be installed in an electronic device. According to the functions implemented, the glycyrrhizic acid antiviral analysis system based on molecular virtual docking can include a viral protein processing module 201, a glycyrrhizic acid processing module 202, a molecular docking processing 203, a binding mode analysis module 204, and an antiviral result analysis module 205. The module of the present invention can also be referred to as a unit, which refers to a series of computer program segments that can be executed by an electronic device processor and can complete fixed functions, which are stored in the memory of the electronic device.

[0076] In the embodiment of the present invention, the functions of each module / unit are as follows: The virus protein processing module 201 is used to obtain the glycyrrhizic acid to be analyzed and its corresponding target virus, identify the key virus protein of the target virus, obtain the three-dimensional structure of the key virus protein, perform conformation optimization processing on the three-dimensional structure, and obtain the target virus protein molecule; The glycyrrhizic acid processing module 202 is used to identify the chemical components of the glycyrrhizic acid, analyze the antiviral properties of the glycyrrhizic acid based on the chemical components, extract the key chemical components of the glycyrrhizic acid according to the antiviral properties, query the three-dimensional chemical structure of the key chemical components, and perform docking pre-processing on the three-dimensional chemical structure based on the target protein molecule to obtain the target glycyrrhizic acid molecule; The molecular docking processing module 203 is used to analyze the functional factors of the key viral protein, wherein the functional factors include virological functional factors and pharmacological functional factors, and determine the molecular docking region between the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, and perform docking processing on the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region to obtain a docking result; A binding mode analysis module 204 is used to identify the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule according to the docking result, analyze the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding mode, calculate the binding free energy between the target glycyrrhizic acid molecule and the target viral protein molecule according to the interaction type, and analyze the affinity between the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding free energy; The antiviral result analysis module 205 is used to determine the target binding mode between the target glycyrrhizic acid molecule and the target viral protein molecule based on the interaction type, the binding free energy and the affinity, and analyze the antiviral effect of the glycyrrhizic acid based on the target binding mode.

[0077] In detail, each module in the glycyrrhizic acid antiviral analysis system 200 based on molecular virtual docking in the embodiment of the present invention is used in the same manner as described above. Figure 1 The method for antiviral analysis of glycyrrhizic acid based on molecular virtual docking described in the present invention has the same technical means and can produce the same technical effects, so it will not be repeated here.

[0078] In addition, each functional module in each embodiment of the present invention may be integrated into one processing unit, each unit may exist physically separately, or two or more units may be integrated into one unit. The above-mentioned integrated unit may be implemented in the form of hardware or in the form of hardware plus software functional modules.

[0079] The above description is only a specific embodiment of the present invention, so that those skilled in the art can understand or implement the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but should conform to the widest scope consistent with the principles and novel features invented herein.

Claims

1. A method for analyzing the antiviral activity of glycyrrhizic acid based on molecular virtual docking, characterized in that: The method comprises: Obtaining glycyrrhizic acid to be analyzed and its corresponding target virus, identifying the key viral protein of the target virus, and obtaining the three-dimensional structure of the key viral protein, performing conformational optimization on the three-dimensional structure, and obtaining the target viral protein molecule; Identify the chemical components of the glycyrrhizic acid, analyze the antiviral properties of the glycyrrhizic acid based on the chemical components, extract the key chemical components of the glycyrrhizic acid based on the antiviral properties, query the three-dimensional chemical structure of the key chemical components, and perform docking pre-processing on the three-dimensional chemical structure based on the target protein molecule to obtain the target glycyrrhizic acid molecule; Analyze the functional factors of the key viral protein, wherein the functional factors include virological functional factors and pharmacological functional factors, determine the molecular docking region of the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, and perform docking processing on the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region to obtain a docking result; According to the docking result, the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule is identified; based on the binding mode, the interaction type between the target glycyrrhizic acid molecule and the target viral protein molecule is analyzed; according to the interaction type, the binding free energy of the target glycyrrhizic acid molecule and the target viral protein molecule is calculated; based on the binding free energy, the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule is analyzed; In combination with the interaction type, the binding free energy and the affinity, the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule is determined, and based on the target binding mode, the antiviral effect of the glycyrrhizic acid is analyzed.

2. The method according to claim 1, characterized in that The step of performing conformational optimization on the three-dimensional structure to obtain a target viral protein molecule comprises: identifying constituent molecules of the three-dimensional structure; Extracting water molecules from the constituent molecules and removing the water molecules to obtain a dehydrated protein structure; The dehydrated protein structure is subjected to hydrogenation treatment to obtain a hydrogenated protein structure.

3. The method according to claim 2, characterized in that The three-dimensional structure is subjected to conformational optimization to obtain a target viral protein molecule, and further comprises: calculating a charge factor of the hydrogenated protein structure; analyzing the atomic types of the hydrogenated protein structure based on the charge factors; According to the atom type, the target viral protein molecule is obtained.

4. The method according to claim 3, characterized in that According to the antiviral properties, the key chemical components of the glycyrrhizic acid are extracted, including: Query the chemical composition of the glycyrrhizic acid; According to the antiviral property, setting an activity evaluation index of the chemical component; Calculating the virus inhibition effect ratio of the chemical component according to the activity evaluation index; Based on the virus inhibition effect ratio, the key chemical components of the glycyrrhizic acid are extracted.

5. The method according to claim 1, characterized in that The analysis of the functional factors of the key viral proteins comprises: Identify the viral species of the key viral protein; analyzing the viral replication cycle of the virus species; Based on the viral replication cycle, identifying the pathogenic mechanism of the key viral protein; The virological functional factors of the key viral proteins are determined in combination with the viral replication cycle and the pathogenic mechanism.

6. The method according to claim 5, characterized in that The analysis of the functional factors of the key viral proteins comprises: Identifying the influencing factors of the pathogenic mechanism and analyzing the viral inhibitory effect of the key viral protein based on the influencing factors; Based on the virus inhibition effect, determining the pharmacological functional factors of the key viral protein; The functional factors of the key viral proteins are analyzed by combining the virological functional factors and the pharmacological functional factors.

7. The method according to claim 1, characterized in that The step of docking the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region includes: Based on the molecular docking region, determining the docking site between the target protein molecule and the target glycyrrhizic acid molecule; Setting the docking file format of the target protein molecule and the target glycyrrhizic acid molecule; According to the docking site, a docking box of the target protein molecule and the target glycyrrhizic acid molecule is set.

8. The method according to claim 7, characterized in that Based on the docking box, defining the docking parameters of the target protein molecule and the target glycyrrhizic acid molecule; In combination with the docking file format and the docking parameters, the target protein molecule and the target glycyrrhizic acid molecule are docked to obtain a docking result.

9. The glycyrrhizic acid antiviral analysis system based on molecular virtual docking is characterized by: The system comprises: A virus protein processing module, used to obtain the glycyrrhizic acid to be analyzed and its corresponding target virus, identify the key virus protein of the target virus, obtain the three-dimensional structure of the key virus protein, perform conformation optimization processing on the three-dimensional structure, and obtain the target virus protein molecule; A glycyrrhizic acid processing module, used to identify the chemical components of the glycyrrhizic acid, analyze the antiviral properties of the glycyrrhizic acid based on the chemical components, extract the key chemical components of the glycyrrhizic acid based on the antiviral properties, query the three-dimensional chemical structure of the key chemical components, and perform docking pre-processing on the three-dimensional chemical structure based on the target protein molecule to obtain the target glycyrrhizic acid molecule; A molecular docking processing module, used to analyze the functional factors of the key viral protein, wherein the functional factors include virological functional factors and pharmacological functional factors, and determine the molecular docking region of the target protein molecule and the target glycyrrhizic acid molecule according to the functional factors, and perform docking processing on the target protein molecule and the target glycyrrhizic acid molecule based on the molecular docking region to obtain a docking result; A binding mode analysis module, for identifying the binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule according to the docking result, analyzing the type of interaction between the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding mode, calculating the binding free energy of the target glycyrrhizic acid molecule and the target viral protein molecule according to the interaction type, and analyzing the affinity of the target glycyrrhizic acid molecule and the target viral protein molecule based on the binding free energy; The antiviral result analysis module is used to determine the target binding mode of the target glycyrrhizic acid molecule and the target viral protein molecule based on the interaction type, the binding free energy and the affinity, and analyze the antiviral effect of the glycyrrhizic acid based on the target binding mode.

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