A method and system for constructing a dynamic electric field of multiple conformations of a biological enzyme

Abstract

The application discloses a kind of biological enzyme multi-conformation dynamic electric field construction method and system, comprising the following steps: obtaining the charge of each atom in biological enzyme system and the spatial position coordinate of each atom in molecular dynamics simulation trajectory multi-conformation;Determine the coordinate of two key atoms of biological enzyme in enzyme catalytic reaction process;Batch submit the file containing biological enzyme molecular dynamics simulation calculation data, calculate the spatial position coordinate of the midpoint of the two key atoms using the midpoint coordinate of two points in space, and use the midpoint as the calculation point, based on the charge of each atom in biological enzyme system, spatial position coordinate, Coulomb constant and the coordinate of the center point of two key atoms, calculate the electric field intensity generated by each part of biological enzyme system to the calculation point using Coulomb law.

Description

Technical Field

[0001] This invention relates to the field of bioenzyme rational modification technology, specifically to a method and system for constructing a dynamic electric field for multiple conformations of bioenzymes. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] Biological enzymes are organic compounds produced by living cells that have catalytic activity; most are proteins, and a small portion is RNA. The electric field characteristics of biological enzymes are considered a crucial factor affecting their catalytic efficiency. Therefore, revealing the dynamic electric field characteristics of multi-conformation biological enzymes is of great significance for the rational design and targeted modification of biological enzymes.

[0004] Currently, electric field data for biological enzymes are typically obtained through manual calculation. However, this method requires a high level of expertise from the personnel performing the calculations, and the results are prone to errors. Furthermore, manual calculations are often time-consuming and cannot be completed quickly enough to calculate the dynamic electric fields of multiple enzyme conformations. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the purpose of this invention is to provide a method and system for constructing a dynamic electric field of biological enzymes with multiple conformations, thereby enabling high-throughput calculation of the changes in the dynamic electric field of biological enzymes with multiple conformations and improving the computational efficiency of the electric field of biological enzymes.

[0006] To achieve the above objectives, the present invention is implemented through the following technical solution:

[0007] In a first aspect, the present invention provides a method for constructing a dynamic electric field for a multiconformation of a biological enzyme, comprising the following steps:

[0008] Obtain the charge and spatial coordinates of each atom in the multi-conformation molecular dynamics simulation trajectory of each atom in the biological enzyme system;

[0009] Determine the coordinates of two key atoms in the enzyme-catalyzed reaction process;

[0010] The system submits files containing molecular dynamics simulation data of biological enzymes in batches. It calculates the spatial coordinates of the midpoint of the two key atoms using the midpoint coordinates of two points in space, and uses this midpoint as the calculation point. Based on the obtained charge, spatial coordinates, Coulomb constant, and coordinates of the center point of the two key atoms in the biological enzyme system, it uses Coulomb's law to calculate and output the electric field intensity generated by each part of the biological enzyme system on the calculation point.

[0011] In some embodiments, the charge and spatial coordinates of each atom in the bioenzyme system include four parts of data: protein residues, solvent environment, reaction substrate, and neutralizing ions.

[0012] In some embodiments, the electric field intensities of different categories of atoms are summed to obtain the electric field intensity value generated by each category of atoms at the calculation point.

[0013] In some embodiments, the simulation duration of bioenzyme molecular dynamics is 20-40 ns, and 10-30 enzyme conformations are randomly selected from the bioenzyme molecular dynamics simulation trajectory.

[0014] Preferably, the simulation duration of bioenzyme molecular dynamics is 30 ns, and 20 enzyme conformations are randomly selected from the bioenzyme molecular dynamics simulation trajectory.

[0015] In some embodiments, the key atom is an atom that undergoes chemical bond formation or chemical bond breaking during the enzyme-catalyzed reaction.

[0016] In some embodiments, the formula for calculating Coulomb's law is:

[0017]

[0018] Where q is the charge of each atom in the biological enzyme system, and k is the coulomb constant. is the vector from each atom to the calculation point, and d is the unit vector along the directions of the two key atoms. The unit of IEF is MV / cm.

[0019] In a second aspect, the present invention provides a system for constructing a dynamic electric field of a bioenzyme multiconformation, including a preprocessing module configured to obtain the charge of each atom in the bioenzyme system and the spatial position coordinates of each atom in the molecular dynamics simulation trajectory multiconformation;

[0020] The key atom selection module is set up to determine the coordinates of two key atoms in the enzyme catalytic reaction process.

[0021] The results output module is set to submit a file containing data from bioenzyme molecular dynamics simulations, and to calculate and output the electric field strength generated by each part of the bioenzyme system at the calculation point.

[0022] Thirdly, the present invention provides a terminal device, including a processor and a memory; the memory is used to store program code and transmit the program code to the processor.

[0023] The processor is configured to execute the method for constructing the multiconformation dynamic electric field of the biological enzyme according to the instructions in the program code.

[0024] Fourthly, the present invention provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the steps of the method for constructing the dynamic electric field of the multiconformation of the biological enzyme.

[0025] The beneficial effects achieved by one or more embodiments of the present invention described above are as follows:

[0026] It has a fast calculation speed and more accurate results, and can quantitatively calculate the electric field strength contributed by each part of the biological enzyme system.

[0027] It requires less manual operation, greatly saving human resources, and the calculation results are less affected by human factors.

[0028] It can perform high-throughput analysis of the electric field intensity of multiple biological enzyme conformations, greatly improving computational efficiency. Attached Figure Description

[0029] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0030] Figure 1 This is a schematic diagram of the calculation process of the present invention.

[0031] Figure 2 This is a flowchart of the batch processing of the present invention. Detailed Implementation

[0032] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0033] Example

[0034] like Figure 1 and Figure 2 As shown, a method for constructing a dynamic electric field for a multi-conformation biological enzyme includes the following steps:

[0035] Step 1: Obtain the charge of each atom in the biological enzyme system to be calculated, as well as the spatial coordinates of each atom in the multi-conformation molecular dynamics simulation trajectory. The atomic charge and spatial coordinates in the biological enzyme molecular dynamics simulation trajectory include data from four parts: protein residues, solvent environment, reaction substrate, and neutralizing ions. Of course, in other embodiments, the charge and spatial coordinate data of the same part of the atoms in the biological enzyme system can be increased or decreased according to specific needs. The biological enzyme molecular dynamics simulation duration is 30 ns, and 20 enzyme conformations are randomly selected from the biological enzyme molecular dynamics simulation trajectory.

[0036] Step 2: Determine the coordinates of two key atoms involved in the enzyme catalytic reaction process. Key atoms refer to the two atoms involved in the formation and breaking of chemical bonds in the biological enzyme catalytic reaction.

[0037] In step 3, molecular dynamics calculation files of the biological enzymes to be tested are submitted in batches, and the input file data is processed using pre-written instructions. Finally, after a series of calculations, the changes in electric field intensity at selected calculation points for different components of multiple enzyme conformations of the biological enzyme are obtained.

[0038] The instructions include calculating the spatial coordinates of the midpoint of two selected key atoms using the midpoint coordinate formula of two points in space, and using this midpoint as the calculation point. Based on the obtained charge, spatial coordinates, Coulomb constant k of each atom in the biological enzyme environment, and coordinates of the center points of the two key atoms, the electric field intensity of each atom in the biological enzyme system along the direction of the two key atoms at the calculation point is obtained using Coulomb's law. The electric fields of each atom are then summed according to their respective classifications.

[0039] The formula for Coulomb's law is as follows:

[0040]

[0041] Where q is the charge of each atom in the biological enzyme system, and k is the coulomb constant. is the vector from each atom to the calculation point, and d is the unit vector along the directions of the two key atoms. The unit of IEF is MV / cm. IEF A positive value indicates that the direction of the electric field is the same as the calculated direction, F IEF A negative value indicates that the direction of the electric field is opposite to the calculated direction.

[0042] A system for constructing a dynamic electric field in a bioenzyme multiformation includes a preprocessing module configured to acquire the charge of each atom in the bioenzyme system and the spatial position coordinates of each atom in the molecular dynamics simulation trajectory multiformation.

[0043] The key atom selection module is set up to determine the coordinates of two key atoms in the enzyme catalytic reaction process.

[0044] The results output module is set to submit a file containing data from bioenzyme molecular dynamics simulations, and to calculate and output the electric field strength generated by each part of the bioenzyme system at the calculation point.

[0045] A terminal device includes a processor and a memory; the memory is used to store program code and transmit the program code to the processor.

[0046] The processor is configured to execute the method for constructing the multiconformation dynamic electric field of the biological enzyme according to the instructions in the program code.

[0047] A computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the steps of the method for constructing the multiconformation dynamic electric field of the biological enzyme.

[0048] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for constructing a dynamic electric field for multiple conformations of a biological enzyme, characterized in that: Includes the following steps: Obtain the charge and spatial coordinates of each atom in the multi-conformation molecular dynamics simulation trajectory of each atom in the biological enzyme system; Determine the coordinates of two key atoms in the enzyme-catalyzed reaction process; Batch submission of files containing bio-enzyme molecular dynamics simulation calculation data; calculation of the spatial position coordinates of the midpoint of the two key atoms using the midpoint coordinates of two points in space; and using the midpoint as the calculation point; based on the obtained charge, spatial position coordinates, Coulomb constant of each atom in the bio-enzyme system and the coordinates of the center point of the two key atoms, using Coulomb's law to calculate and output the electric field intensity generated by each part of the bio-enzyme system on the calculation point. The key atom is an atom that undergoes chemical bond formation or breakage during the enzyme-catalyzed reaction.

2. The method for constructing a dynamic electric field for a multiconformation of a biological enzyme according to claim 1, characterized in that: The charge and spatial coordinates of each atom in a biological enzyme system include data from four parts: protein residues, solvent environment, reaction substrate, and neutralizing ions.

3. The method for constructing a dynamic electric field for a multiconformation of a biological enzyme according to claim 1, characterized in that: The electric field intensities of different categories of atoms are summed to obtain the electric field intensity value generated by each category of atoms at the calculation point.

4. The method for constructing a dynamic electric field for a multiconformation of a biological enzyme according to claim 1, characterized in that: The simulation duration for bioenzyme molecular dynamics is 20-40 ns, and 10-30 enzyme conformations are randomly selected from the bioenzyme molecular dynamics simulation trajectory.

5. The method for constructing a dynamic electric field for a multiconformation of a biological enzyme according to claim 4, characterized in that: The simulation duration for bioenzyme molecular dynamics was 30 ns, and 20 enzyme conformations were randomly selected from the bioenzyme molecular dynamics simulation trajectory.

6. The method for constructing a dynamic electric field for a multiconformation of a biological enzyme according to claim 1, characterized in that: The formula for Coulomb's law is: ； in, q It represents the charge of each atom in the biological enzyme system, and k is the coulomb constant. It is a vector from each atom to the computation point. d It is a unit vector along the directions of the two key atoms.

7. A system for constructing a dynamic electric field for a multiconformation of a biological enzyme, characterized in that: It includes a preprocessing module, which is set up to obtain the charge of each atom in the biological enzyme system and the spatial position coordinates of each atom in the multi-conformation of molecular dynamics simulation trajectories; The key atom selection module is set up to determine the coordinates of two key atoms in the enzyme catalytic reaction process. The results output module is set to submit a file containing bio-enzyme molecular dynamics simulation calculation data. It calculates the spatial position coordinates of the midpoint of the two key atoms using the midpoint coordinates of two points in space, and uses this midpoint as the calculation point. Based on the obtained charge, spatial position coordinates, Coulomb constant of each atom in the bio-enzyme system and the coordinates of the center point of the two key atoms, it uses Coulomb's law to calculate and output the electric field intensity generated by each part of the bio-enzyme system on the calculation point. The key atom is an atom that undergoes chemical bond formation or chemical bond breakage during the enzyme-catalyzed reaction.

8. A terminal device, characterized in that: It includes a processor and a memory; the memory is used to store program code and transfer the program code to the processor; The processor is configured to execute the method for constructing the multiconformation dynamic electric field of any one of claims 1-6 according to the instructions in the program code.

9. A computer-readable storage medium, characterized in that: It stores a computer program that, when executed by a processor, implements the steps of the method for constructing the multiconformation dynamic electric field of the biological enzyme as described in any one of claims 1-6.

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