Method for obtaining charge parameters, method and device for molecular mechanics simulation results

Abstract

The present application discloses a method for obtaining charge parameters, a method and device for molecular mechanics simulation results, and the method for obtaining charge parameters includes: obtaining the initial electrostatic potential charge of the target molecule; constructing a simulation system based on the target molecule and multiple environmental molecules; using the initial electrostatic potential charge to perform molecular dynamics simulation on the simulation system to at least obtain the coordinate information of the environmental molecules at multiple moments; obtaining the first electrostatic potential charge of the target molecule based on the coordinate information of the environmental molecules at multiple moments and the charge amount of each atom in the environmental molecules; judging whether the first electrostatic potential charge and the initial electrostatic potential charge meet the first preset condition; if so, using the first electrostatic potential charge as the charge parameter of the target molecule when it is surrounded by environmental molecules. In the above manner, the present application can obtain the charge parameters by considering the environment in which the solvent molecules are located, so as to improve the accuracy of the molecular mechanics simulation results of the solvent molecules in the environment in which they are located.

Description

Technical Field

[0001] The present application belongs to the field of molecular simulation technology, and specifically relates to a method for obtaining charge parameters, a method and a device for molecular mechanics simulation results. Background Art

[0002] Molecular mechanics, which is based on classical mechanics, has a wide range of applications in many fields due to its speed advantage, such as drug design and material design. Molecular force field is an indispensable component of molecular mechanics, and the quality of the parameters in the molecular force field directly determines the accuracy of the molecular mechanics simulation results. The traditional molecular force field contains bonding terms (e.g., bond length, bond angle, dihedral angle, etc.) and non-bonding terms (e.g., charge interaction, van der Waals interaction, etc.). In the process of non-covalent drug molecules and protein molecules binding, non-bonding terms, especially charge interaction, play a vital role.

[0003] The calculation of charge interactions using molecular force fields requires charge parameters in the force field, and the point charge model is currently commonly used to calculate the charge parameters. The general way to obtain point charges is based on the gas phase, that is, a single molecule is obtained by fitting the spatial potential generated by quantum chemical methods in an isolated environment. However, in real biological application scenarios, the processes that need to be simulated are often in solutions (usually water) or protein environments. These environments will affect the potential distribution of the small molecules themselves, resulting in a spatial potential that is different from that in the gas phase. That is, the charge parameters obtained by fitting in the gas phase may lead to inaccurate results in actual complex environments. Summary of the invention

[0004] The present application provides a method for obtaining charge parameters, a method and an apparatus for molecular mechanics simulation results, which obtain charge parameters by fitting the environment in which the solute molecules are located, so as to improve the accuracy of the molecular mechanics simulation results of the solute molecules in the environment in which they are located.

[0005] In order to solve the above technical problems, a technical solution adopted in the present application is: providing a method for obtaining charge parameters, including: S1, structural optimization of solute molecules to obtain at least one target molecule, and obtaining the initial electrostatic potential charge of each target molecule; S2, for each target molecule, constructing a simulation system based on the target molecule and multiple environmental molecules; wherein the target molecule is surrounded by multiple environmental molecules; S3, using the initial electrostatic potential charge to perform molecular dynamics simulation on the simulation system to at least obtain the coordinate information of the environmental molecules at multiple times during the simulation process; S4, based on the coordinate information of the environmental molecules at multiple times and the charge amount of each atom in the environmental molecules, obtain the first electrostatic potential charge of the target molecule; S5, judging whether the first electrostatic potential charge and the initial electrostatic potential charge meet the first preset condition; S6, if so, taking the first electrostatic potential charge as the charge parameter of the target molecule when it is surrounded by the environmental molecules; S7, otherwise, taking the first electrostatic potential charge as the initial electrostatic potential charge and returning to step S3.

[0006] In order to solve the above technical problems, another technical solution adopted in the present application is: to provide a method for obtaining molecular mechanics simulation results, comprising: obtaining the charge parameters of the solute molecules using the method described in any of the above embodiments; and obtaining the molecular mechanics simulation results of the solute molecules and the environmental molecules based on the charge parameters.

[0007] In order to solve the above technical problems, another technical solution adopted by the present application is: to provide a device for obtaining charge parameters, including: a first obtaining module, used to perform structural optimization on the solute molecules to obtain at least one target molecule, and obtain the initial electrostatic potential charge of each target molecule; a building module, connected to the first obtaining module, used to construct a simulation system based on the target molecule and multiple environmental molecules for each target molecule; wherein the target molecule is surrounded by multiple environmental molecules; a second obtaining module, connected to the building module, used to perform molecular dynamics simulation on the simulation system using the initial electrostatic potential charge, so as to at least obtain the coordinate information of the environmental molecules at multiple moments during the simulation process; a third obtaining module, connected to the building module A second acquisition module is connected, and is used to obtain the first electrostatic potential charge of the target molecule based on the coordinate information of the environmental molecules at multiple moments and the charge of each atom in the environmental molecules; a judgment module is connected to the third acquisition module, and is used to judge whether the first electrostatic potential charge and the initial electrostatic potential charge meet a first preset condition; an execution module is connected to the judgment module, and is used to use the first electrostatic potential charge as the charge parameter of the target molecule when the target molecule is surrounded by the environmental molecules when the judgment module judges to be yes; and is used to use the first electrostatic potential charge as the initial electrostatic potential charge and return to the step of performing molecular dynamics simulation on the simulation system using the initial electrostatic potential charge when the judgment module judges to be no.

[0008] In order to solve the above-mentioned technical problems, another technical solution adopted in the present application is: to provide an electronic device, comprising a memory and a processor coupled to each other, wherein the memory stores program instructions, and the processor is used to execute the program instructions to implement the method for obtaining charge parameters described in any of the above-mentioned embodiments, or the method for obtaining molecular mechanics simulation results.

[0009] In order to solve the above technical problems, another technical solution adopted in the present application is: providing a storage device storing program instructions that can be run by a processor, and the processor is used to execute the program instructions to implement the method for obtaining charge parameters described in any of the above embodiments, or the method for obtaining molecular mechanics simulation results.

[0010] Different from the prior art, the beneficial effect of the present application is that the process of the method for obtaining charge parameters of the present application includes: optimizing the structure of the solute molecule to obtain at least one target molecule, and obtaining the initial electrostatic potential charge of each target molecule; for each target molecule, constructing a simulation system based on the target molecule and multiple environmental molecules; wherein the target molecule is surrounded by multiple environmental molecules; using the initial electrostatic potential charge to perform molecular dynamics simulation on the simulation system to at least obtain the coordinate information of the environmental molecules at multiple moments during the simulation process; based on the coordinate information of the environmental molecules at multiple moments and the charge of each atom in the environmental molecule, obtain the first electrostatic potential charge of the target molecule; determine whether the first electrostatic potential charge and the initial electrostatic potential charge meet the first preset condition; if so, use the first electrostatic potential charge as the charge parameter of the target molecule when it is surrounded by the environmental molecules; otherwise, use the first electrostatic potential charge as the initial electrostatic potential charge and return to the step of performing molecular dynamics simulation on the simulation system using the initial electrostatic potential charge. In the above manner, the present application considers the influence of environmental molecules on the charge parameters of solute molecules to improve the accuracy of molecular mechanics simulation results of solute molecules in their environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the description of the embodiments are briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without creative work, among which:

[0012] Figure 1 A schematic diagram of a flow chart of an implementation method of obtaining charge parameters according to the present application;

[0013] Figure 2 for Figure 1 A schematic flow chart of an embodiment of performing structural optimization on a solute molecule to obtain at least one target molecule in step S1;

[0014] Figure 3 for Figure 1 A schematic flow chart of an embodiment of performing structural optimization on a solute molecule to obtain at least one target molecule in step S1;

[0015] Figure 4 for Figure 1 A schematic flow chart of an implementation method corresponding to step S3;

[0016] Figure 5 for Figure 1 A schematic diagram of a flow chart of an implementation method corresponding to step S4;

[0017] Figure 6 A schematic diagram of a process for obtaining molecular mechanics simulation results according to an embodiment of the present invention;

[0018] Figure 7 A schematic structural diagram of an embodiment of a device for obtaining charge parameters of the present application;

[0019] Figure 8 This is a schematic diagram of the structure of an embodiment of an electronic device of the present application;

[0020] Fig. 9 This is a schematic structural diagram of an implementation of a storage device of the present application. DETAILED DESCRIPTION

[0021] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0022] See also Figure 1 , Figure 1 This is a flow chart of an embodiment of a method for obtaining charge parameters in the present application, the method comprising:

[0023] S1: Structural optimization of solute molecules is performed to obtain at least one target molecule, and an initial electrostatic potential charge of each target molecule is obtained.

[0024] Specifically, in one embodiment, see Figure 2 , Figure 2 for Figure 1 Schematic diagram of a process of optimizing the structure of the solute molecule to obtain at least one target molecule in step S1. The process of optimizing the structure of the solute molecule to obtain at least one target molecule in step S1 specifically includes:

[0025] S201: Constructing an implicit solvent model based on multiple environmental molecules.

[0026] Optionally, the environmental molecules may include organic solvent molecules or inorganic solvent molecules or protein molecules, etc.; wherein the organic solvent molecules include methanol, ethanol, benzene, ether, dichloromethane, acetone, tetrahydrofuran, ethyl acetate, acetonitrile or toluene, etc.; the inorganic solvent molecules include water, ammonia, hydrogen fluoride, or sulfur dioxide, etc. The above only lists a few common solvent molecules. In other embodiments, the corresponding environmental molecules can be selected according to the actual application scenario; and in the actual application scenario, the environmental molecules are generally cited one by one, that is, the environmental molecule can be one of the molecules listed above. Alternatively, the implicit solvent model may be Onsager model, PCM (Polarizable continuum model), CPCM (conductor-like polarizable continuum model), IPCM (isodensity polarizable continuum model), SCIPCM (self-consistent isodensity polarizable continuum model), COSMO (conductor-like screening model), SMD (solvation model based on density), etc.

[0027] In simple terms, the implicit solvent model treats the solvent molecules (i.e., environmental molecules) as a continuous medium. That is, it does not specifically describe the specific structure and distribution of environmental molecules near the solute molecules, but simply considers the surrounding environment as a polarizable continuous medium. The advantage of considering the solvent effect is that it can show the average effect of the solvent without considering the various possible arrangements of the solvent layer molecules as in the explicit solvent model, and it does not increase the computational time significantly.

[0028] S202: Place the solute molecules in the implicit solvent model for structural optimization to obtain the target molecules with the lowest local energy.

[0029] Alternatively, the Hartree-Fock (HF) method in an open source quantum chemical calculation software (such as NWChem, GAMESS, Gaussian, etc.) can be used for structural optimization to obtain a target molecule with the lowest local energy. Taking NWChem software as an example, when operating the NWChem software, the keyword "task hf energy" can be directly selected to obtain the target molecule.

[0030] Furthermore, after obtaining the target molecule, the initial electrostatic potential (ESP) charge Q of the target molecule can be obtained using current quantum chemical calculation software. 0 , and the coordinates of each atom in the target molecule. Taking NWChem software as an example, when operating NWChem software, you can directly select the keyword "task esp" to obtain the initial electrostatic potential charge Q of the target molecule. 0 .

[0031] In another embodiment, when the molecular structure of the solute molecule is relatively large, it may include multiple conformations. In this case, corresponding target molecules can be obtained for different conformations to improve the accuracy of the charge parameters of the solute molecule obtained subsequently. Figure 3 , Figure 3 for Figure 1 Schematic diagram of a process of optimizing the structure of the solute molecule to obtain at least one target molecule in step S1. The process of optimizing the structure of the solute molecule to obtain at least one target molecule in step S1 specifically includes:

[0032] S301: Perform dihedral rotation on the solute molecules to obtain multiple molecules with different conformations.

[0033] Specifically, it is known from common knowledge that the change of conformation does not involve the change of covalent bonds, and the difference between molecules with different conformations lies only in the difference in three-dimensional structure.

[0034] S302: Structural optimization is performed on each conformational molecule to obtain a corresponding optimized structural molecule.

[0035] Specifically, the implementation process of the above step S302 can be: first, construct an implicit solvent model based on multiple environmental molecules; this step is similar to the above step S201 and will not be described in detail here. Then, place the conformational molecule in the implicit solvent model for structural optimization to obtain the target molecule with the lowest local energy; this step is similar to the above step S202 and will not be described in detail here.

[0036] S303: Merge the molecules with the same stereostructure among all the optimized structural molecules to obtain at least one target molecule.

[0037] Alternatively, the three-dimensional structures of the optimized structural molecules corresponding to all conformational molecules may be the same, in which case the number of target molecules finally obtained after merging is one. For example, the conformational molecules formed after dihedral rotation of the solute molecule A include A, A1, A2, and A3, and the optimized structural molecules corresponding to the conformational molecules A, A1, A2, and A3 are all B, so the target molecule is B at this time.

[0038] Alternatively, the three-dimensional structures of the optimized structural molecules corresponding to all conformational molecules may include at least two, and the number of target molecules finally obtained after merging is at least two. For example, the conformational molecules formed after the dihedral rotation of the solute molecule A include A, A1, A2, and A3, and the optimized structural molecules corresponding to the conformational molecules A and A1 are both B, and the optimized structural molecules corresponding to the conformational molecules A2 and A3 are both B1, then the target molecules are B and B1.

[0039] S2: For each target molecule, a simulation system is constructed based on the target molecule and multiple environmental molecules; wherein the target molecule is surrounded by multiple environmental molecules.

[0040] Specifically, in one embodiment, the step of constructing a simulation system based on a target molecule and a plurality of environmental molecules in the above step S2 includes: constructing an explicit solvent model based on a plurality of environmental molecules; placing the target molecule in the explicit solvent model to obtain a simulation system. Optionally, the above explicit solvent model can be TIP3P (transferable intermolecular potential 3point, a 3-point model of transferable intermolecular potential), TIP4P (transferable intermolecular potential 4point, a 4-point model of transferable intermolecular potential), TIP5P (transferable intermolecular potential 5point, a 5-point model of transferable intermolecular potential), etc. The explicit solvent model is a model that simulates each solvent molecule (i.e., environmental molecule) as a separate molecule; that is, each environmental molecule in the explicit solvent model is a separate molecule, and the use of the explicit solvent model can consider the influence of each atom in the environmental molecule on the charge parameters of the solute molecule to improve the accuracy of the charge parameters obtained subsequently.

[0041] S3: Perform molecular dynamics simulation on the simulation system using the initial electrostatic potential charge to at least obtain coordinate information of the environmental molecules at multiple moments during the simulation process.

[0042] Specifically, see Figure 4 , Figure 4 for Figure 1 The flowchart of an implementation method corresponding to step S3 in FIG. 1 is a flowchart of an implementation method corresponding to step S3 in FIG. 1 , wherein step S3 specifically includes:

[0043] S401: Initialize the molecular dynamics model using initial electrostatic potential charges.

[0044] Specifically, the dynamics model built into the molecular dynamics software GROMACS can be used for dynamics simulation; and the charge parameter in the dynamics model is the initial electrostatic potential charge Q 0 .

[0045] S402: Performing dynamic simulation on the simulation system based on the initialized molecular dynamics model, and during the simulation process, the coordinates of each atom in the target molecule are kept unchanged, and only the coordinates of each atom in the environment molecule are allowed to change.

[0046] Optionally, in this embodiment, the coordinates of each atom in the target molecule may be the same as the coordinates of the target molecule obtained in step S1; that is, the position of the target molecule in step S1 and step S3 may be kept unchanged.

[0047] S403: within a predetermined simulation time range, save the coordinates of each atom in all environmental molecules at the current moment at predetermined time intervals.

[0048] Optionally, the predetermined simulation time range may be 2 nanoseconds, and the predetermined time interval may be 10 picoseconds, in which case the coordinates of each atom in all environmental molecules at 200 moments may be obtained.

[0049] The above-mentioned method of keeping the coordinates of each atom in the target molecule unchanged can make the method of obtaining the first electrostatic potential charge in the subsequent step S4 simpler and less computationally intensive.

[0050] S4: Obtaining a first electrostatic potential charge of the target molecule based on the coordinate information of the environmental molecules at multiple moments and the charge of each atom in the environmental molecules.

[0051] Optionally, when the coordinates of each atom of the target molecule are kept unchanged in step S3, refer to Figure 5 , Figure 5 for Figure 1 The above step S4 specifically includes:

[0052] S501: The coordinates of each atom in all environmental molecules at each moment are used as the coordinates of multiple point charges outside the target molecule, and the second ratio of the charge amount of each atom in all environmental molecules at each moment to the number at multiple moments is used as the charge amount of the point charge at the corresponding position.

[0053] For example, there are 100 environmental molecules around the current solute molecule, and the charge of each atom in the environmental molecules can be the same or different. For example, when the environmental molecules are water molecules, each water molecule has 3 atoms, the charge of the oxygen atom in the water molecule is -0.8, and the charge of the hydrogen atom in the water molecule is 0.4. Then there are 3*100 point charges in the current environment at the same time. When the coordinates of the environmental molecules at 200 moments are obtained in step S3, there are 300*200=60000 point charges in common around the current solvent molecules, and the charge at each point charge position is the charge of the atom corresponding to the point charge coordinate divided by 200.

[0054] S502: Obtain a first electrostatic potential charge based on the coordinates of a plurality of point charges outside the target molecule and their charge amounts.

[0055] Alternatively, the first electrostatic potential charge Q1 may be obtained by single point energy calculation and fitting using a quantum chemical HF method.

[0056] Alternatively, when the position of the target molecule also moves during the kinetic simulation in step S3, the position of the simulation system at multiple moments can be moved first, and the target molecule and the environmental molecules in the simulation system will move synchronously. When the position of the target molecule at each moment is the same, step S501 is entered.

[0057] S5: Determine whether the first electrostatic potential charge and the initial electrostatic potential charge meet a first preset condition.

[0058] Specifically, the specific implementation process of the above step S5 may be: judging whether the average variance between the first electrostatic potential charge Q1 and the initial electrostatic potential charge Q0 is less than a threshold; optionally, the threshold may be 0.01, etc. This design method has a small amount of calculation.

[0059] Of course, in other embodiments, the specific implementation process of the above step S5 may also be: determining whether the standard deviation between the first electrostatic potential charge Q1 and the initial electrostatic potential charge Q0 is less than a threshold value, which is not limited in the present application.

[0060] S6: If yes, use the first electrostatic potential charge as a charge parameter when the target molecule is surrounded by environmental molecules.

[0061] S7: Otherwise, the first electrostatic potential charge is used as the initial electrostatic potential charge, and the process returns to step S3.

[0062] In the above design method, the influence of environmental molecules on the charge parameters of solute molecules is considered to improve the accuracy of the molecular mechanics simulation results of solute molecules in the environment. In addition, in general, the implicit solvent model has a faster calculation rate, but the accuracy is worse than that of the explicit solvent model; the explicit solvent model has higher accuracy than the implicit solvent model when considering the interaction between solute molecules and solvent molecules, but it consumes more computing resources and has a slower calculation efficiency. In this application, in step S1, the implicit solvent model with a fast calculation rate but not so high accuracy is first used for calculation, and then the explicit solvent model with a slow calculation rate but high accuracy is used for calculation, which can improve the effect of the entire method, including efficiency and accuracy. In addition, when the number of target molecules obtained in step S1 is at least two, after the above step S7, it can also include: obtaining the sum of the charge parameters corresponding to all target molecules; using the first ratio of the sum value to the number of target molecules as the charge parameter of the solute molecule when it is surrounded by environmental molecules. This design method can further improve the accuracy of the charge parameters of the solute molecules.

[0063] See also Figure 6 , Figure 6 This is a flow chart of a method for obtaining molecular mechanics simulation results according to an embodiment of the present invention. The method specifically includes:

[0064] S601: Obtain the charge parameters of the solute molecules.

[0065] Optionally, in this embodiment, the implementation process of the above step S601 may refer to the method for obtaining the charge parameter mentioned in any of the above embodiments.

[0066] S602: Obtain molecular mechanics simulation results of solute molecules and environmental molecules based on charge parameters.

[0067] In an application scenario, when the charge parameters obtained in step S601 are used to calculate some solvation-related properties such as hydration free energy (i.e., the free energy required for a molecule to dissolve in water from the gas phase), the first result obtained is closer to the experimental value than the second result obtained by calculating the charge parameters obtained using the gas phase method.

[0068] For example, the method for obtaining charge parameters provided in this application is applied to the Freesolv data set, and the charge parameters in the force field (generated by the AM1-BCC model) are replaced by Figure 1The process in the present invention takes into account the charge parameters of the water environment, while retaining other parameters in the force field. The average variance between the calculated hydration free energy and the experimental value is 1.12 kcal / mol. When the charge parameters are obtained by the gas phase method, the average variance between the calculated hydration free energy and the experimental value is 1.51 kcal / mol. The smaller variance indicates that the calculated value and the experimental value are more consistent. The new charge parameter acquisition process provided in this application brings more accurate calculated values.

[0069] See also Figure 7 , Figure 7 This is a structural schematic diagram of an embodiment of a device for obtaining charge parameters of the present application. The device for obtaining charge parameters includes a first obtaining module 10, a construction module 12, a second obtaining module 14, a third obtaining module 16, a judgment module 18 and an execution module 11.

[0070] Among them, the first acquisition module 10 is used to optimize the structure of the solute molecules to obtain at least one target molecule, and obtain the initial electrostatic potential charge of each target molecule. The construction module 12 is connected to the first acquisition module 10, and is used to construct a simulation system based on the target molecule and multiple environmental molecules for each target molecule; wherein the target molecule is surrounded by multiple environmental molecules. The second acquisition module 14 is connected to the construction module 12, and is used to perform molecular dynamics simulation on the simulation system using the initial electrostatic potential charge to at least obtain the coordinate information of the environmental molecules at multiple moments during the simulation process. The third acquisition module 16 is connected to the second acquisition module 14, and is used to obtain the first electrostatic potential charge of the target molecule based on the coordinate information of the environmental molecules at multiple moments and the charge amount of each atom in the environmental molecule. The judgment module 18 is connected to the third acquisition module 16, and is used to judge whether the first electrostatic potential charge and the initial electrostatic potential charge meet the first preset condition. The execution module 11 is connected to the judgment module 18, and is used to use the first electrostatic potential charge as the charge parameter when the target molecule is surrounded by environmental molecules when the judgment module judges to be yes; and to use the first electrostatic potential charge as the initial electrostatic potential charge and return to the step of performing molecular dynamics simulation on the simulation system using the initial electrostatic potential charge when the judgment module judges to be no.

[0071] Optionally, the first acquisition module 10 is specifically used to construct an implicit solvent model based on multiple environmental molecules; the solute molecules are placed in the implicit solvent model for structural optimization to obtain the target molecule with the lowest local energy. Alternatively, the first acquisition module 10 is specifically used to perform dihedral rotation on the solute molecules to obtain multiple different conformational molecules; perform structural optimization on each conformational molecule to obtain the corresponding optimized structure molecule; and merge the same stereoscopic structure molecules in all optimized structure molecules to obtain at least one target molecule.

[0072] Alternatively, the construction module 12 is specifically used to construct an explicit solvent model based on multiple environmental molecules; the target molecule is placed in the explicit solvent model to obtain a simulation system.

[0073] Alternatively, the second acquisition module 14 is specifically used to initialize the molecular dynamics model using the initial electrostatic potential charge; perform dynamic simulation on the simulation system based on the initialized molecular dynamics model, and keep the coordinates of each atom in the target molecule unchanged during the simulation, and only allow the coordinates of each atom in the environmental molecules to change; within a predetermined simulation time range, save the coordinates of each atom in all environmental molecules at the current moment at predetermined time intervals.

[0074] Alternatively, the third acquisition module 16 is specifically used to use the coordinates of each atom in all environmental molecules at each moment as the coordinates of multiple point charges outside the target molecule, and use the second ratio of the charge of each atom in all environmental molecules at each moment to the number at multiple moments as the charge of the point charge at the corresponding position; and obtain the first electrostatic potential charge based on the coordinates of the multiple point charges outside the target molecule and their charge amounts.

[0075] Alternatively, the judgment module 18 is specifically configured to judge whether the average square error between the first electrostatic potential charge and the initial electrostatic potential charge is less than a threshold value.

[0076] In addition, when the number of target molecules is at least two, the above-mentioned device can also include a fourth acquisition module, which is connected to the execution module 18, and is used to obtain the sum of the charge parameters corresponding to all target molecules; and use the first ratio of the sum to the number of target molecules as the charge parameter when the solute molecule is surrounded by environmental molecules.

[0077] See also Figure 8 , Figure 8The schematic diagram of the structure of an embodiment of an electronic device of the present application, the electronic device comprises: a memory 22 and a processor 20 coupled to each other, a program instruction is stored in the memory 22, and the processor 20 is used to execute the program instruction to realize any of the above-mentioned methods for obtaining charge parameters, or the method for obtaining the results of molecular mechanics simulation. Specifically, the electronic device includes but is not limited to: a desktop computer, a laptop computer, a tablet computer, a server, etc., which are not limited here. In addition, the processor 20 can also be referred to as a CPU (Center Processing Unit). The processor 20 may be an integrated circuit chip with signal processing capabilities. The processor 20 may also be a general-purpose processor, a digital signal processor (DigitalSignal Processor, DSP), an application-specific integrated circuit (Application Specific Integrated Circuit, ASIC), a field-programmable gate array (Field-Programmable Gate Array, FPGA) or other programmable logic devices, discrete gates or transistor logic devices, discrete hardware components. The general-purpose processor may be a microprocessor or the processor may also be any conventional processor, etc. In addition, the processor 20 may be implemented by an integrated circuit chip.

[0078] See also Fig. 9 , Fig. 9 This is a schematic diagram of the structure of an embodiment of a storage device of the present application. The storage device 30 stores program instructions 300 that can be executed by a processor. The program instructions 300 are used to implement any of the above-mentioned methods for obtaining charge parameters or methods for obtaining molecular mechanics simulation results.

[0079] In the several embodiments provided in the present application, it should be understood that the disclosed methods and devices can be implemented in other ways. For example, the device implementation described above is only schematic. For example, the division of modules or units is only a logical function division. There may be other division methods in actual implementation, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some interfaces, and the indirect coupling or communication connection of devices or units can be electrical, mechanical or other forms.

[0080] The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the present embodiment.

[0081] In addition, each functional unit in each embodiment of the present application may be integrated into one processing unit, or 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 software functional units.

[0082] If the integrated unit is implemented in the form of a software functional unit and sold or used as an independent product, it can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present application is essentially or the part that contributes to the prior art or all or part of the technical solution can be embodied in the form of a software product, and the computer software product is stored in a storage medium, including a number of instructions to enable a computer device (which can be a personal computer, server, or network device, etc.) or a processor (processor) to perform all or part of the steps of each implementation method of the present application. The aforementioned storage medium includes: U disk, mobile hard disk, read-only memory (ROM, Read-Only Memory), random access memory (RAM, Random Access Memory), disk or optical disk and other media that can store program code.

[0083] The above description is only an embodiment of the present application and does not limit the patent scope of the present application. Any equivalent structure or equivalent process transformation made using the contents of the present application specification and drawings, or directly or indirectly used in other related technical fields, are also included in the patent protection scope of the present application.

Claims

1. A method for obtaining charge parameters, It is characterized in that include: S1. Optimizing the structure of the solute molecules to obtain at least one target molecule, and obtaining the initial electrostatic potential charge of each target molecule; S2. For each target molecule, construct a simulation system based on the target molecule and a plurality of environmental molecules; wherein the target molecule is surrounded by a plurality of environmental molecules; S3, performing molecular dynamics simulation on the simulation system using the initial electrostatic potential charge, so as to at least obtain coordinate information of the environmental molecules at multiple moments during the simulation process; S4, obtaining a first electrostatic potential charge of the target molecule based on the coordinate information of the environmental molecule at multiple moments and the charge of each atom in the environmental molecule; S5, determining whether the first electrostatic potential charge and the initial electrostatic potential charge meet a first preset condition; S6. If yes, use the first electrostatic potential charge as a charge parameter when the target molecule is surrounded by the environmental molecules; S7. Otherwise, use the first electrostatic potential charge as the initial electrostatic potential charge, and return to step S3.

2. The method according to claim 1, It is characterized in that The step of optimizing the structure of the solute molecule to obtain at least one target molecule comprises: constructing an implicit solvent model based on a plurality of said environmental molecules; The solute molecule is placed in the implicit solvent model for structural optimization to obtain the target molecule with the lowest local energy.

3. The method according to claim 1, It is characterized in that The step of optimizing the structure of the solute molecule to obtain at least one target molecule comprises: performing dihedral rotation on the solute molecule to obtain a plurality of molecules with different conformations; Performing structural optimization on each of the conformational molecules to obtain a corresponding optimized structure molecule; The same stereostructure molecules among all the optimized structure molecules are merged to obtain at least one target molecule.

4. The method according to claim 3, It is characterized in that The number of the target molecules is at least two, and the method further comprises: Obtaining the sum of the charge parameters corresponding to all the target molecules; A first ratio of the sum value to the number of the target molecules is used as a charge parameter when the solute molecules are surrounded by the environmental molecules.

5. The method according to claim 1, It is characterized in that The step of constructing a simulation system based on the target molecule and a plurality of environmental molecules comprises: constructing an explicit solvent model based on a plurality of said environmental molecules; The target molecule is placed in the explicit solvent model to obtain a simulation system.

6. The method according to claim 1, It is characterized in that The step of using the initial electrostatic potential charge to perform molecular dynamics simulation on the simulation system to at least obtain coordinate information of the environmental molecules at multiple moments during the simulation process includes: Initializing a molecular dynamics model using the initial electrostatic potential charge; Performing dynamic simulation on the simulation system based on the initialized molecular dynamics model, and keeping the coordinates of each atom in the target molecule unchanged during the simulation, and only allowing the coordinates of each atom in the environmental molecule to change; Within a predetermined simulation time range, the coordinates of each atom in all the environment molecules at the current moment are saved at predetermined time intervals.

7. The method according to claim 6, It is characterized in that The step of obtaining the first electrostatic potential charge of the target molecule based on the coordinate information of the environmental molecules at multiple moments and the charge of each atom in the environmental molecules comprises: Taking the coordinates of each atom in all the environmental molecules at each moment as the coordinates of multiple point charges outside the target molecule, and taking the second ratio of the charge amount of each atom in all the environmental molecules at each moment to the number of the multiple moments as the charge amount of the point charge at the corresponding position; The first electrostatic potential charge is obtained by fitting based on the coordinates of the plurality of point charges outside the target molecule and their charge amounts.

8. The method according to claim 1, It is characterized in that The step of determining whether the first electrostatic potential charge and the initial electrostatic potential charge meet a first preset condition comprises: It is determined whether an average square difference between the first electrostatic potential charge and the initial electrostatic potential charge is less than a threshold.

9. The method according to claim 1, It is characterized in that The environmental molecules include organic solvent molecules or inorganic solvent molecules or protein molecules; wherein the organic solvent molecules include methanol, ethanol, benzene, ether, dichloromethane, acetone, tetrahydrofuran, ethyl acetate, acetonitrile or toluene; the inorganic solvent molecules include water, ammonia, hydrogen fluoride, or sulfur dioxide.

10. A method for obtaining molecular mechanics simulation results, It is characterized in that include: Obtaining the charge parameter of the solute molecule using the method described in any one of claims 1 to 9; The molecular mechanics simulation results of the solute molecules and the environmental molecules are obtained based on the charge parameters.

11. A device for obtaining charge parameters, It is characterized in that include: A first acquisition module is used to perform structural optimization on the solute molecules to obtain at least one target molecule, and obtain the initial electrostatic potential charge of each of the target molecules; A construction module, connected to the first acquisition module, for constructing a simulation system for each target molecule based on the target molecule and a plurality of environmental molecules; wherein the target molecule is surrounded by a plurality of the environmental molecules; A second acquisition module, connected to the construction module, is used to perform molecular dynamics simulation on the simulation system using the initial electrostatic potential charge to at least obtain coordinate information of the environmental molecules at multiple moments during the simulation process; A third acquisition module, connected to the second acquisition module, is used to obtain the first electrostatic potential charge of the target molecule based on the coordinate information of the environmental molecules at multiple moments and the charge of each atom in the environmental molecules; A judging module, connected to the third obtaining module, for judging whether the first electrostatic potential charge and the initial electrostatic potential charge meet a first preset condition; An execution module is connected to the judgment module and is used for, when the judgment module judges as yes, using the first electrostatic potential charge as the charge parameter when the target molecule is surrounded by the environmental molecules; and when the judgment module judges as no, using the first electrostatic potential charge as the initial electrostatic potential charge and returning to the step of performing molecular dynamics simulation on the simulation system using the initial electrostatic potential charge.

12. An electronic device, It is characterized in that It comprises a memory and a processor coupled to each other, wherein the memory stores program instructions, and the processor is used to execute the program instructions to implement the method for obtaining charge parameters as described in any one of claims 1 to 9, or the method for obtaining molecular mechanics simulation results as described in claim 10.

13. A storage device, It is characterized in that Program instructions that can be executed by a processor are stored, and the processor is used to execute the program instructions to implement the method for obtaining charge parameters described in any one of claims 1 to 9, or the method for obtaining molecular mechanics simulation results described in claim 10.

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