Intermolecular interaction conformation generation method and device based on electrostatic potential matching

Abstract

The invention discloses an intermolecular interaction conformation generation method and device based on electrostatic potential matching, and relates to the field of theory and computational chemistry, and the method comprises the steps: calculating a 3D conformation of a set molecule through a quantum chemistry strategy to obtain wave function information of a molecular system; calculating the set molecules according to the electron density value to obtain the electron density value of the set molecules; constructing Van der Waals surfaces of the set molecules by constructing a contour surface strategy; by setting a potential calculation strategy, calculating electrostatic potential values of grid points on the set molecule Van der Waals surface; through setting an orientation confirmation strategy, determining mutual approaching orientations of a plurality of set molecules in pairs; 3D conformations of a plurality of set molecules are obtained by setting a public data set or geometric structure optimization processing, and the non-covalent interaction conformation is formed by splicing every two set molecules through a set splicing strategy according to the orientation that every two set molecules are close to each other. According to the method, the intermolecular non-covalent interaction conformation can be quickly and accurately obtained.

Description

Technical Field

[0001] The present invention relates to the technical field of theoretical and computational chemistry, and in particular to a method and device for generating intermolecular interaction conformations based on electrostatic potential matching. Background Art

[0002] In the past few decades, quantum chemical calculation methods have made great progress. For a chemical system, people can now obtain quite accurate calculation results through quantum chemical calculations. One of the most important application areas is the calculation and research of non-covalent interaction systems, which plays an important role in chemistry, biology, and materials science.

[0003] Unlike covalent bonds, non-covalent interactions do not involve electron sharing between atoms. They are mainly electromagnetic interactions between or within molecules. The energy of non-covalent interactions is usually very small, only 1~5 kcal / mol. Hydrogen bonds are also usually considered non-covalent interactions. The energy of some hydrogen bonds is very large, reaching the order of tens of kcal / mol, but still less than the strength of ordinary chemical bonds. For general polar molecules, non-covalent interactions are usually dominated by electrostatic interactions. Electrostatic interactions are of vital importance in the formation of various self-assembled nanostructures, providing stable and strong interactions between various enzymes, peptides and proteins. For a molecular system, due to the different electronegativity of each atom in its structure and the chemical environment in which it is located, the distribution of electrons on it is also uneven, with more electrons distributed in some places and less electrons distributed in some places. In areas with higher electron density, the value of electrostatic potential is also more negative, and vice versa. Generally, areas with more negative electrostatic potential values ​​are called nucleophilic areas, and areas with more positive electrostatic potential values ​​are called electrophilic areas. When two molecules approach each other, the nucleophilic region of one molecule tends to attract the electrophilic region of the other molecule (the same is true inside a flexible molecule).

[0004] At present, non-covalent interactions are widely present in nature, especially playing an important role in the chemical reaction process in organisms. Non-covalent interactions are essential for maintaining the three-dimensional structure of molecules such as proteins and nucleic acids. At the same time, they also have very important applications in drug design, material crystallization and design, and material self-assembly. To calculate the energy of non-covalent interactions, the most important thing is to obtain the conformation of intermolecular interactions, and then select appropriate quantum chemical calculation methods to calculate the interaction energy based on this conformation.

[0005] Therefore, it is very important to quickly and accurately obtain the conformation of non-covalent interactions between molecules so that researchers can immediately study the corresponding chemical system. Summary of the invention

[0006] To this end, the present invention provides a method and device for generating intermolecular interaction conformations based on electrostatic potential matching, which can give the specific location of intermolecular non-covalent interactions through the distribution of molecular surface electrostatic potential, and based on the specific location of intermolecular non-covalent interactions, quickly and accurately obtain the conformation of intermolecular non-covalent interactions.

[0007] In order to achieve the above object, the present invention provides the following technical solution: a method for generating intermolecular interaction conformations based on electrostatic potential matching, comprising: Calculating the 3D conformation of a set molecule through a quantum chemical strategy to obtain wave function information of the molecular system; calculating the set molecule based on the wave function information to obtain the electron density value of the set molecule; The set molecule is calculated by constructing an isosurface strategy to construct a van der Waals surface of the set molecule; and the electrostatic potential value of the grid point on the van der Waals surface of the set molecule is calculated by setting an electric potential calculation strategy; According to the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule, by setting the orientation confirmation strategy, determining the orientations of the plurality of the set molecules approaching each other; By setting a public data set or geometric structure optimization processing, the 3D conformations of the set molecules are obtained; the 3D conformations of the set molecules are spliced ​​in pairs according to the orientations in which the set molecules approach each other, by setting a splicing strategy, to form non-covalent interaction conformations.

[0008] As a preferred scheme of the method for generating conformation of intermolecular interactions based on electrostatic potential matching, in the process of calculating the 3D conformation of the set molecule through the quantum chemical strategy, the quantum chemical strategy includes: a post-Hartree-Fock strategy based on wave function, a density functional theory strategy based on electron density, and a semi-empirical strategy.

[0009] As a preferred solution of the method for generating conformations of intermolecular interactions based on electrostatic potential matching, in the process of calculating the set molecule according to the wave function information to obtain the electron density value of the set molecule, it is necessary to calculate the electron density at each location in the set molecule space through a grid point construction strategy; the calculation formula for the electron density of any grid point in the set molecule space is: ; ; In the formula, is the electron density; is the orbital occupancy number; is the orbital expansion coefficient; 、 、 are the components of the three directions of the Cartesian coordinates of the grid point; 、 、 is the exponent of the Gaussian basis function; is the base of natural logarithms; is the distance from the grid point to the coordinate origin; is the exponential factor.

[0010] As a preferred scheme of the method for generating conformations of intermolecular interactions based on electrostatic potential matching, in the process of calculating the set molecule through the isosurface construction strategy to construct the van der Waals surface of the set molecule, the isosurface construction strategy includes: surface network strategy, asymptotic decision strategy and cube marching strategy.

[0011] As a preferred embodiment of the method for generating conformations of intermolecular interactions based on electrostatic potential matching, in the process of calculating the electrostatic potential values ​​of the lattice points on the van der Waals surface of the set molecule through the set public data set or the geometric structure optimization process, the calculation formula of the set potential calculation strategy is: ; In the formula, For molecular systems The electrostatic potential at express The nuclear charge of the atom; is the distance between the grid point to be calculated and the coordinate origin; for The location of atoms; for The integral part is expressed as the electron density of the entire space relative to the position Do the points.

[0012] As a preferred scheme of the method for generating intermolecular interaction conformations based on electrostatic potential matching, in the process of determining the orientations of a number of set molecules approaching each other by means of the set orientation confirmation strategy, the set orientation confirmation strategy includes: an atomic van der Waals surface strategy and a van der Waals surface random point sampling strategy.

[0013] As a preferred embodiment of the method for generating intermolecular interaction conformations based on electrostatic potential matching, in the process of splicing the 3D conformations of several set molecules in pairs through the set splicing strategy to form a non-covalent interaction conformation, the set splicing strategy includes: Rodrigues rotation matrix strategy, automatic action site screening strategy and interaction fusion strategy.

[0014] The present invention also provides an intermolecular interaction conformation generation device based on electrostatic potential matching, based on the above intermolecular interaction conformation generation method based on electrostatic potential matching, comprising: The electron density value acquisition module is used to calculate the 3D conformation of the set molecule through quantum chemical strategy to obtain the wave function information of the molecular system; according to the wave function information, the set molecule is calculated to obtain the electron density value of the set molecule; The module for obtaining the electrostatic potential value of the van der Waals surface is used to calculate the set molecule by constructing an isosurface strategy to construct the van der Waals surface of the set molecule; and to calculate and obtain the electrostatic potential value of the grid point on the van der Waals surface of the set molecule by setting the potential calculation strategy; A module for determining the direction in which molecules approach each other, for determining the direction in which a plurality of the set molecules approach each other by setting a direction confirmation strategy according to the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule; The molecular splicing processing module is used to obtain the 3D conformations of several set molecules by setting a public data set or geometric structure optimization processing; the 3D conformations of several set molecules are spliced ​​in pairs according to the orientation of the set molecules approaching each other, by setting a splicing strategy, to form a non-covalent interaction conformation.

[0015] As a preferred solution of the intermolecular interaction conformation generation device based on electrostatic potential matching, in the electron density numerical acquisition module, in the process of calculating the 3D conformation of the set molecule through the quantum chemical strategy, the quantum chemical strategy includes: a post-Hartree-Fock strategy based on wave function, a density functional theory strategy based on electron density, and a semi-empirical strategy.

[0016] As a preferred solution of the intermolecular interaction conformation generation device based on electrostatic potential matching, in the electron density value acquisition module, in the process of calculating the set molecule according to the wave function information and obtaining the electron density value of the set molecule, it is necessary to calculate the electron density at each location in the set molecule space through the strategy of constructing grid points; the calculation formula of the electron density of any grid point in the set molecule space is: ; ; In the formula, is the electron density; is the orbital occupancy number; is the orbital expansion coefficient; 、 、 are the components of the three directions of the Cartesian coordinates of the grid point; 、 、 is the exponent of the Gaussian basis function; is the base of natural logarithms; is the distance from the grid point to the coordinate origin; is the exponential factor.

[0017] As a preferred solution of the intermolecular interaction conformation generation device based on electrostatic potential matching, in the electrostatic potential numerical acquisition module of the van der Waals surface, in the process of calculating the set molecule through the isosurface construction strategy to construct the van der Waals surface of the set molecule, the isosurface construction strategy includes: surface network strategy, asymptotic decision strategy and cube marching strategy.

[0018] As a preferred solution of the intermolecular interaction conformation generation device based on electrostatic potential matching, in the electrostatic potential value acquisition module of the van der Waals surface, in the process of calculating the electrostatic potential value of the grid point on the van der Waals surface of the set molecule through the set public data set or the geometric structure optimization process, the calculation formula of the set potential calculation strategy is: ; In the formula, For molecular systems The electrostatic potential at express The nuclear charge of the atom; is the distance between the grid point to be calculated and the coordinate origin; for The location of atoms; for The integral part is expressed as the electron density of the entire space relative to the position Do the points.

[0019] As a preferred solution of the intermolecular interaction conformation generation device based on electrostatic potential matching, in the module for determining the direction of approach between molecules, in the process of determining the directions of approach between a number of set molecules by means of the set direction confirmation strategy, the set direction confirmation strategy includes: atomic van der Waals surface strategy and van der Waals surface random point sampling strategy.

[0020] As a preferred solution of the intermolecular interaction conformation generation device based on electrostatic potential matching, in the molecular splicing processing module, in the process of splicing the 3D conformations of several set molecules in pairs through the set splicing strategy to form a non-covalent interaction conformation, the set splicing strategy includes: Rodrigues rotation matrix strategy, automatic action site screening strategy and interaction fusion strategy.

[0021] The present invention has the following advantages: the 3D conformation of the set molecule is calculated by quantum chemical strategy to obtain the wave function information of the molecular system; according to the wave function information, the set molecule is calculated to obtain the electron density value of the set molecule; the set molecule is calculated by constructing an isosurface strategy to construct the van der Waals surface of the set molecule; the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule is calculated by setting an electric potential calculation strategy; according to the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule, the orientation of the approaching of several set molecules is determined by setting an orientation confirmation strategy; by setting a public data set or geometric structure optimization processing, the 3D conformation of several set molecules is obtained; the 3D conformation of several set molecules is spliced ​​in pairs according to the orientation of the approaching of the set molecules in pairs, by setting a splicing strategy, to form a non-covalent interaction conformation. The present invention can give the specific position of the non-covalent interaction between molecules by the distribution of the electrostatic potential on the molecular surface. The conformation formed by the relative position with a greater positive and negative difference in the intermolecular electrostatic potential has a greater probability of appearing in all intermolecular non-covalent interaction conformations, and the absolute value of its interaction energy is also the largest. At the same time, the present invention can also be applied in the study of chemical reaction mechanisms, and can provide a reasonable initial guess of the mechanism for the chemical system under study, can indicate some directions, and reduce the trial and error cost in the study of chemical reaction mechanisms. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the implementation methods of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for the implementation methods or the description of the prior art. Obviously, the drawings in the following description are only exemplary, and for ordinary technicians in this field, other implementation drawings can be derived from the provided drawings without creative work.

[0023] The structures, proportions, sizes, etc. illustrated in this specification are only used to match the contents disclosed in the specification so as to facilitate understanding and reading by persons familiar with the technology. They are not used to limit the conditions under which the present invention can be implemented, and therefore have no substantial technical significance. Any structural modification, change in proportion or adjustment in size shall still fall within the scope of the technical contents disclosed in the present invention without affecting the effects and purposes that can be achieved by the present invention.

[0024] Figure 1 This is a schematic flow chart of the method for generating intermolecular interaction conformations based on electrostatic potential matching provided in Example 1 of the present invention; Figure 2 This is a schematic diagram of the distribution of electrostatic potential values ​​corresponding to each grid point on the van der Waals surface of a dimethyl sulfide molecule in a possible embodiment provided in Example 1 of the present invention; Figure 3 A schematic diagram of the distribution of electrostatic potential values ​​corresponding to each grid point on the van der Waals surface of an ethanol molecule in a possible embodiment provided in Example 1 of the present invention; Figure 4 A schematic diagram of a non-covalent interaction conformation generated in a possible embodiment provided in Example 1 of the present invention; Figure 5 Schematic diagram of the architecture of the device for generating conformation of intermolecular interactions based on electrostatic potential matching provided in Example 2 of the present invention. DETAILED DESCRIPTION

[0025] The following is a description of the implementation of the present invention by specific embodiments. People familiar with the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] Example 1 See also Figure 1 Embodiment 1 of the present invention provides a method for generating intermolecular interaction conformations based on electrostatic potential matching, comprising the following steps: S1. Calculate the 3D conformation of a set molecule by quantum chemical strategy to obtain wave function information of the molecular system; calculate the set molecule according to the wave function information to obtain the electron density value of the set molecule; S2, calculating the set molecule by constructing an isosurface strategy to construct a van der Waals surface of the set molecule; calculating and obtaining the electrostatic potential value of the grid point on the van der Waals surface of the set molecule by setting an electric potential calculation strategy; S3, determining the directions in which the plurality of the set molecules approach each other by setting a direction confirmation strategy according to the electrostatic potential values ​​of the lattice points on the van der Waals surface of the set molecule; S4. Obtaining the 3D conformations of several of the set molecules by setting a public data set or geometric structure optimization processing; splicing the 3D conformations of several of the set molecules in pairs according to the orientations in which the set molecules approach each other by setting a splicing strategy to form a non-covalent interaction conformation.

[0027] In this embodiment, in step S1, the 3D conformation of the set molecule is calculated by quantum chemical strategy to obtain the wave function information of the molecular system; The quantum chemical strategies include, but are not limited to, post-Hartree-Fock strategies based on wave functions, density functional theory (DFT) strategies based on electron density, and semi-empirical strategies.

[0028] In this embodiment, the set molecule is calculated according to the wave function information to obtain the electron density value of the set molecule; Specifically, after calculating the wave function information of the molecular system, the electron density value at any point in space can be further calculated from the wave function information. The electron density at each point in space needs to be calculated by constructing a grid. The molecule is wrapped with a rectangular prism to determine the size of the entire molecule. The three sides of the rectangular prism are divided into grid points, and the number of segments divided on the three sides is , and , then the number of grid points into which the entire rectangular prism is divided is The more grid points there are, the more computation is required, and vice versa.

[0029] The calculation formula for the electron density of any grid point in the set molecular space is: ; ; In the formula, is the electron density; is the orbital occupancy number; is the orbital expansion coefficient; 、 、 are the components of the three directions of the Cartesian coordinates of the grid point; 、 、 is the exponent of the Gaussian basis function; is the base of natural logarithms; is the distance from the grid point to the coordinate origin; is the exponential factor.

[0030] In this embodiment, in step S2, the set molecule is calculated by constructing an isosurface strategy to construct a van der Waals surface of the set molecule; Specifically, the definition of van der Waals surface: According to Bader's definition of van der Waals surface, it is an isosurface formed by the electron density around the molecule of 0.001 au. In order to obtain the van der Waals surface, the method of constructing isosurfaces in computational graphics can be used, including but not limited to the use of surface nets method, asymptotic decider method, marching cubes method and other methods.

[0031] In this embodiment, the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule is calculated by setting the potential calculation strategy; Specifically, after constructing the van der Waals surface, it is necessary to calculate the electrostatic potential value of the grid points on the van der Waals surface. The calculation formula of the electrostatic potential is: ; In the formula, For molecular systems The electrostatic potential at express The nuclear charge of the atom; is the distance between the grid point to be calculated and the coordinate origin; for The location of atoms; for The integral part is expressed as the electron density of the entire space relative to the position Do the points.

[0032] In this embodiment, in step S3, the directions in which the plurality of the set molecules approach each other are determined by setting a direction confirmation strategy according to the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule; Specifically, after obtaining the electrostatic potential values ​​of each lattice point on the van der Waals surfaces of the two molecules, it is necessary to determine the orientation of the two molecules approaching each other. The orientation confirmation strategy includes but is not limited to: atomic van der Waals surface method, van der Waals surface random point sampling method, etc.

[0033] In this embodiment, in step S4, the 3D conformations of the set molecules are obtained by setting a public data set or geometric structure optimization processing; the 3D conformations of the set molecules are spliced ​​in pairs according to the orientations in which the set molecules approach each other, by setting a splicing strategy, to form non-covalent interaction conformations.

[0034] Specifically, for the two molecules to be studied, their molecular 3D conformations must first be obtained, which can be obtained from public data sets or by performing geometric structure optimization using quantum chemistry software including but not limited to Gaussian, ORCA, Q-Chem, etc.

[0035] According to the orientation of the two molecules approaching each other, the 3D conformations of the two molecules are spliced ​​to form a non-covalent interaction conformation. The splicing strategy includes but is not limited to: Rodrigues rotation matrix method, automated interaction site screening method, interaction fusion method, etc.

[0036] In one possible embodiment, an example of generating a non-covalent interaction conformation of dimethyl sulfide-ethanol molecules is provided as follows: The molecular formula of dimethyl sulfide is CH3SCH3; the molecular formula of ethanol is CH3CH2OH T1. Constructing grid points: For dimethyl sulfide molecules, The final number of grid points in the three directions is 64, 53, and 56, so the total number of grid points is 189952. For ethanol molecules, The final grid number numerators in the three directions are 60, 51, and 48, so the total number of grid points is 146,800.

[0037] T2. Calculate the electron density: Use the formula to calculate the electron density of the two molecules above at different grid points Data, set the threshold For 10 -4 , that is, select |ρ-0.001|<10 -4 The grid points of are used as the grid points for the subsequent determination of the van der Waals surface.

[0038] T3. Use the Marching Cubes method to construct the molecular van der Waals surface. Each small cube obtained in step T2 is further divided into 6 tetrahedrons to more accurately approximate the surface. T4. Perform the following operations on each tetrahedron: a. Check the 8 vertices of the tetrahedron. b. Determine which edges intersect with the isosurface. c. Calculate the location of the intersection. d. Generate triangular patches based on the intersection.

[0039] T5. Use linear interpolation to determine the intersection of the isosurface and the edge. The interpolation formula used is: ; in, and are the two endpoints of the edge, and is the corresponding electron density value.

[0040] T6. Generate 0 to 2 triangles based on the intersection of the tetrahedron and the isosurface, and add the generated triangles to the output mesh.

[0041] T7. Merge duplicate vertices and use smoothing to improve the quality of the generated surface, and finally obtain a van der Waals surface represented by a triangular mesh.

[0042] T8. Calculate the electrostatic potential value of the van der Waals surface grid. The van der Waals surfaces of dimethyl sulfide and ethanol molecules are finally obtained, such as Figure 2 As shown; the numerical distribution of electrostatic potential corresponding to each grid point on the van der Waals surface is as follows Figure 3 shown.

[0043] T9. Use the method of dividing the van der Waals surface into different atoms: different positions of the van der Waals surface are assigned to different atoms according to the following weight formula: ; in, To divide into The weight on the atom, and They are The distance and radius of the atom from the origin of the coordinate system, is the distance from any point in space to the origin of the coordinate system. The van der Waals surface is therefore divided into multiple parts, each of which is attributed to the corresponding atom.

[0044] T10. Count the extreme points of the electrostatic potential on each part of the van der Waals surface. The extreme points are either positive or negative. A positive extreme point indicates that the area near the atom to which it belongs is an electrophilic region, and a negative extreme point indicates that the area near the atom to which it belongs is a nucleophilic region. The Cartesian coordinates of the extreme points of the electrostatic potential of dimethyl sulfide and ethanol molecules are recorded in Table 1, which are divided into positive extreme points and negative extreme points. Matching the positive extreme points of the dimethyl sulfide molecule with the negative extreme points of ethanol, and matching the negative extreme points of the dimethyl sulfide molecule with the positive extreme points of ethanol, will result in a total of 6×2+2×4=20 molecular conformations.

[0045] Table 1 Cartesian coordinates of the extreme points of electrostatic potential of dimethyl sulfide and ethanol molecules

[0046] T11. Given two molecular structures, first use the Cartesian coordinate system of the dimethyl sulfide molecule as the standard, move the ethanol molecule into this coordinate system and keep a certain distance from the dimethyl sulfide molecule to ensure that there is no intersection between them. According to the extreme points of the electrostatic potential of the two molecules obtained in step T10, the molecular orientation vectors of the two molecules are determined. It can be seen from step T10 that a total of 20 molecular conformations will be obtained by matching the electrostatic potential. Fix the dimethyl sulfide molecule, and use the Rodrigues rotation matrix to rotate the ethanol molecule according to the obtained vector so that it is parallel and opposite to the vector of the water molecule. When the relative vectors of the two molecules are aligned, the distance between the two molecules is shortened along the direction of this vector until a reasonable position is reached. As shown in FIG. Figure 4 As shown, all 20 generated conformations are displayed.

[0047] In summary, the present invention calculates the 3D conformation of the set molecule by quantum chemical strategy to obtain the wave function information of the molecular system; according to the wave function information, the set molecule is calculated to obtain the electron density value of the set molecule; the set molecule is calculated by constructing an isosurface strategy to construct the van der Waals surface of the set molecule; the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule is calculated by setting an electric potential calculation strategy; according to the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule, the orientation of the approaching direction of several set molecules is determined by setting a direction confirmation strategy; by setting a public data set or geometric structure optimization processing, the 3D conformation of several set molecules is obtained; the 3D conformation of several set molecules is spliced ​​in pairs according to the orientation of the approaching direction of the set molecules, and the splicing strategy is set to form a non-covalent interaction conformation. The present invention can give the specific position of the non-covalent interaction between molecules by the distribution of the electrostatic potential on the molecular surface. The conformation formed by the relative position with a greater positive and negative difference in the intermolecular electrostatic potential has a greater probability of appearing in all intermolecular non-covalent interaction conformations, and the absolute value of its interaction energy is also the largest. At the same time, the present invention can also be applied in the study of chemical reaction mechanisms, and can provide a reasonable initial guess of the mechanism for the chemical system under study, can indicate some directions, and reduce the trial and error cost in the study of chemical reaction mechanisms.

[0048] It should be noted that the method of the embodiment of the present disclosure can be performed by a single device, such as a computer or a server. The method of the present embodiment can also be applied in a distributed scenario and completed by multiple devices cooperating with each other. In the case of such a distributed scenario, one of the multiple devices can only perform one or more steps in the method of the embodiment of the present disclosure, and the multiple devices will interact with each other to complete the described method.

[0049] It should be noted that some embodiments of the present disclosure are described above. In some cases, the actions or steps recorded can be performed in an order different from that in the above embodiments and still achieve the desired results. In addition, the processes depicted in the accompanying drawings do not necessarily require the specific order or continuous order shown to achieve the desired results. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0050] Example 2 See also Figure 5 Embodiment 2 of the present invention also provides a device for generating conformation of intermolecular interactions based on electrostatic potential matching, comprising: The electron density value acquisition module 001 is used to calculate the 3D conformation of the set molecule through quantum chemical strategy to obtain the wave function information of the molecular system; according to the wave function information, the set molecule is calculated to obtain the electron density value of the set molecule; The electrostatic potential value acquisition module 002 of the van der Waals surface is used to calculate the set molecule by constructing an isosurface strategy to construct the van der Waals surface of the set molecule; and to calculate and obtain the electrostatic potential value of the grid point on the van der Waals surface of the set molecule by setting the potential calculation strategy; The module 003 for determining the approach direction between molecules is used to determine the approach directions between a plurality of the set molecules according to the electrostatic potential values ​​of the lattice points on the van der Waals surfaces of the set molecules and by setting a direction confirmation strategy; The molecular splicing processing module 004 is used to obtain the 3D conformations of the set molecules by setting a public data set or geometric structure optimization processing; the 3D conformations of the set molecules are spliced ​​in pairs according to the orientation of the set molecules approaching each other, by setting a splicing strategy, to form a non-covalent interaction conformation.

[0051] In this embodiment, in the electron density numerical acquisition module 001, in the process of calculating the 3D conformation of the set molecule through the quantum chemical strategy, the quantum chemical strategy includes: a post-Hartree-Fock strategy based on wave function, a density functional theory strategy based on electron density, and a semi-empirical strategy.

[0052] In this embodiment, in the electron density value acquisition module 001, in the process of calculating the set molecule according to the wave function information to obtain the electron density value of the set molecule, it is necessary to calculate the electron density at each location in the set molecule space by constructing a grid point strategy; the calculation formula for the electron density of any grid point in the set molecule space is: ; ; In the formula, is the electron density; is the orbital occupancy number; is the orbital expansion coefficient; 、 、 are the components of the three directions of the Cartesian coordinates of the grid point; 、 、 is the exponent of the Gaussian basis function; is the base of natural logarithms; is the distance from the grid point to the coordinate origin; is the exponential factor.

[0053] In this embodiment, in the module 002 for acquiring the electrostatic potential numerical value of the van der Waals surface, in the process of calculating the set molecule through the isosurface construction strategy to construct the van der Waals surface of the set molecule, the isosurface construction strategy includes: surface network strategy, asymptotic decision strategy and cube marching strategy.

[0054] In this embodiment, in the electrostatic potential value acquisition module 002 of the van der Waals surface, in the process of calculating the electrostatic potential value of the grid point on the van der Waals surface of the set molecule through the set public data set or the geometric structure optimization process, the calculation formula of the set potential calculation strategy is: ; In the formula, For molecular systems The electrostatic potential at express The nuclear charge of the atom; is the distance between the grid point to be calculated and the coordinate origin; for The location of atoms; for The integral part is expressed as the electron density of the entire space relative to the position Do the points.

[0055] In this embodiment, in the module 003 for determining the direction of approach between molecules, in the process of determining the directions of approach between a number of set molecules by using the set direction confirmation strategy, the set direction confirmation strategy includes: atomic van der Waals surface strategy and van der Waals surface random point sampling strategy.

[0056] In this embodiment, in the molecular splicing processing module 004, in the process of splicing the 3D conformations of the set molecules in pairs through the set splicing strategy to form a non-covalent interaction conformation, the set splicing strategy includes: Rodrigues rotation matrix strategy, automatic action site screening strategy and interaction fusion strategy.

[0057] It should be noted that the information interaction, execution process and other contents between the modules of the above-mentioned system are based on the same concept as the method embodiment in Example 1 of the present application, and the technical effects they bring are the same as those of the method embodiment of the present application. For specific contents, please refer to the description in the method embodiment shown above in the present application, and will not be repeated here.

[0058] Example 3 Embodiment 3 of the present invention provides a non-transitory computer-readable storage medium, in which a program code for a method for generating conformations of intermolecular interactions based on electrostatic potential matching is stored, and the program code includes instructions for executing the method for generating conformations of intermolecular interactions based on electrostatic potential matching of embodiment 1 or any possible implementation thereof.

[0059] Computer-readable storage media can be any available medium that can be accessed by a computer or a data storage device such as a server or data center that includes one or more available media. The available medium can be a magnetic medium (e.g., a floppy disk, a hard disk, a tape), an optical medium (e.g., a DVD), or a semiconductor medium (e.g., a solid-state drive (SSD)).

[0060] Example 4 Embodiment 4 of the present invention provides an electronic device, including: a memory and a processor; The processor and the memory communicate with each other via a bus; the memory stores program instructions that can be executed by the processor, and the processor calls the program instructions to execute the intermolecular interaction conformation generation method based on electrostatic potential matching of Example 1 or any possible implementation thereof.

[0061] Specifically, the processor can be implemented by hardware or by software. When implemented by hardware, the processor can be a logic circuit, an integrated circuit, etc.; when implemented by software, the processor can be a general-purpose processor implemented by reading software codes stored in a memory. The memory can be integrated in the processor or can be located outside the processor and exist independently.

[0062] In the above embodiments, it can be implemented in whole or in part by software, hardware, firmware or any combination thereof. When implemented using software, it can be implemented in whole or in part in the form of a computer program product. The computer program product includes one or more computer instructions. When the computer program instructions are loaded and executed on a computer, the process or function described in the embodiment of the present invention is generated in whole or in part. The computer can be a general-purpose computer, a special-purpose computer, a computer network, or other programmable systems. The computer instructions can be stored in a computer-readable storage medium, or transmitted from a computer-readable storage medium to another computer-readable storage medium, for example, the computer instructions can be transmitted from a website site, computer, server or data center by wired (e.g., coaxial cable, optical fiber, digital subscriber line (DSL)) or wireless (e.g., infrared, wireless, microwave, etc.) mode to another website site, computer, server or data center.

[0063] Obviously, those skilled in the art should understand that the above modules or steps of the present invention can be implemented by a general computing system, they can be concentrated on a single computing system, or distributed on a network composed of multiple computing systems, and optionally, they can be implemented by a program code executable by a computing system, so that they can be stored in a storage system and executed by the computing system, and in some cases, the steps shown or described can be executed in a different order than here, or they can be made into individual integrated circuit modules, or multiple modules or steps therein can be made into a single integrated circuit module for implementation. Thus, the present invention is not limited to any specific combination of hardware and software.

[0064] Although the present invention has been described in detail above by general description and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A method for generating conformation of intermolecular interactions based on electrostatic potential matching, characterized in that: include: Calculating the 3D conformation of a set molecule through a quantum chemical strategy to obtain wave function information of the molecular system; calculating the set molecule based on the wave function information to obtain the electron density value of the set molecule; The set molecule is calculated by constructing an isosurface strategy to construct a van der Waals surface of the set molecule; and the electrostatic potential value of the grid point on the van der Waals surface of the set molecule is calculated by setting an electric potential calculation strategy; According to the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule, by setting the orientation confirmation strategy, determining the orientations of the plurality of the set molecules approaching each other; By setting a public data set or geometric structure optimization processing, the 3D conformations of the set molecules are obtained; the 3D conformations of the set molecules are spliced ​​in pairs according to the orientations in which the set molecules approach each other, by setting a splicing strategy, to form non-covalent interaction conformations.

2. The method for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 1, characterized in that: In the process of calculating the 3D conformation of the set molecule by the quantum chemical strategy, the quantum chemical strategy includes: a post-Hartree-Fock strategy based on wave function, a density functional theory strategy based on electron density, and a semi-empirical strategy.

3. The method for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 2, characterized in that: In the process of calculating the set molecule according to the wave function information and obtaining the electron density value of the set molecule, it is necessary to calculate the electron density at each location in the set molecule space by constructing a grid point strategy; the calculation formula for the electron density of any grid point in the set molecule space is: ； ； In the formula, is the electron density; is the orbital occupancy number; is the orbital expansion coefficient; 、 、 are the components of the three directions of the Cartesian coordinates of the grid point; 、 、 is the exponent of the Gaussian basis function; is the base of natural logarithms; is the distance from the grid point to the coordinate origin; is the exponential factor.

4. The method for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 3, characterized in that: In the process of calculating the set molecule by using the isosurface construction strategy to construct the van der Waals surface of the set molecule, the isosurface construction strategy includes: surface network strategy, asymptotic decision strategy and cube marching strategy.

5. The method for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 4, characterized in that: In the process of calculating the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule by using the set potential calculation strategy, the calculation formula of the set potential calculation strategy is: ； In the formula, For molecular systems The electrostatic potential at express The nuclear charge of the atom; is the distance between the grid point to be calculated and the coordinate origin; for The location of atoms; for The electron density at The integral part is expressed as the electron density in the entire space relative to the position Do the points.

6. The method for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 5, characterized in that: In the process of determining the directions in which the set molecules approach each other by using the set direction confirmation strategy, the set direction confirmation strategy includes: an atomic van der Waals surface strategy and a van der Waals surface random point sampling strategy.

7. The method for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 6, characterized in that: In the process of splicing the 3D conformations of several set molecules in pairs to form non-covalent interaction conformations through the set public data set or the geometric structure optimization processing, the set splicing strategy includes: Rodrigues rotation matrix strategy, automatic action site screening strategy and interaction fusion strategy.

8. A device for generating conformation of intermolecular interactions based on electrostatic potential matching, using the method for generating conformation of intermolecular interactions based on electrostatic potential matching according to any one of claims 1 to 7, characterized in that: include: The electron density value acquisition module is used to calculate the 3D conformation of the set molecule through quantum chemical strategy to obtain the wave function information of the molecular system; according to the wave function information, the set molecule is calculated to obtain the electron density value of the set molecule; The module for obtaining the electrostatic potential value of the van der Waals surface is used to calculate the set molecule by constructing an isosurface strategy to construct the van der Waals surface of the set molecule; and to calculate and obtain the electrostatic potential value of the grid point on the van der Waals surface of the set molecule by setting the potential calculation strategy; A module for determining the direction in which molecules approach each other, for determining the direction in which a plurality of the set molecules approach each other by setting a direction confirmation strategy according to the electrostatic potential value of the lattice point on the van der Waals surface of the set molecule; The molecular splicing processing module is used to obtain the 3D conformations of several set molecules by setting a public data set or geometric structure optimization processing; the 3D conformations of several set molecules are spliced ​​in pairs according to the orientation of the set molecules approaching each other, by setting a splicing strategy, to form a non-covalent interaction conformation.

9. The device for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 8, characterized in that: In the electron density value acquisition module, in the process of calculating the set molecule according to the wave function information to obtain the electron density value of the set molecule, it is necessary to calculate the electron density at each location in the set molecule space by constructing a grid point strategy; the calculation formula for the electron density of any grid point in the set molecule space is: ； ； In the formula, is the electron density; is the orbital occupancy number; is the orbital expansion coefficient; 、 、 are the components of the three directions of the Cartesian coordinates of the grid point; 、 、 is the exponent of the Gaussian basis function; is the base of natural logarithms; is the distance from the grid point to the coordinate origin; is the exponential factor.

10. The device for generating conformation of intermolecular interactions based on electrostatic potential matching according to claim 9, characterized in that: In the van der Waals surface electrostatic potential value acquisition module, in the process of calculating the electrostatic potential value of the grid point on the van der Waals surface of the set molecule by using the set potential calculation strategy, the calculation formula of the set potential calculation strategy is: ； In the formula, For molecular systems The electrostatic potential at express The nuclear charge of the atom; is the distance between the grid point to be calculated and the coordinate origin; for The location of atoms; for The electron density at The integral part is expressed as the electron density in the entire space relative to the position Do the points.

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