Methods for determining the forces that perturb a molecule's conformation

Abstract

The present application discloses a method for determining the force of a disturbed molecular conformation, which belongs to the field of molecular mechanics, including: obtaining a conformational sequence of a molecule, and mechanical perturbation data of the molecule; determining a first initial conformation and a second initial conformation in the conformational sequence according to a target moment; applying mechanical perturbation data to the first initial conformation to obtain a perturbed conformation; using the first initial conformation and the second initial conformation as sampling data of a local Gaussian distribution, determining the variance of the local Gaussian distribution and the steady-state conformation of the molecule; determining the conservative force to which the perturbed conformation of the molecule is subjected at the target moment according to the variance, the perturbed conformation, and the steady-state conformation. The present application is based on the principle of the local Gaussian distribution obeyed by the initial conformations at two adjacent moments, and solves the problem of the complexity of obtaining the data basis and the high computing power requirements of the computing equipment in the calculation process of the force in molecular dynamics simulation.

Description

Technical Field

[0001] The present application belongs to the field of molecular mechanics, and specifically relates to a method, device, electronic device and computer-readable storage medium for determining the force of a disturbed molecular conformation. Background Art

[0002] In the field of molecular dynamics research, researchers often need to simulate the dynamic behavior of molecules to predict and analyze the reactions and changes of molecules in different environments. These simulations are crucial for new drug development, material science, and understanding the functions of biological molecules such as proteins and genetic sequences.

[0003] In the prior art, molecular dynamics simulations usually rely on classical force field methods or density functional theory (DFT) that can provide an accurate description of interatomic forces to calculate the forces on molecules in various conformations.

[0004] However, the accuracy of classical force field methods relies on force field parameters, which often need to be adjusted for specific types of molecules; while DFT methods are computationally expensive and very sensitive to the choice of underlying data. Summary of the invention

[0005] The present application aims to provide a method, device, electronic device and computer-readable storage medium for determining the force of a disturbed molecular conformation, which at least solves the problem of the complexity of obtaining the data basis and the high computing power requirements of the computing device in the process of calculating the force in molecular dynamics simulation.

[0006] In a first aspect, the present application discloses a method for determining the force of disturbing the conformation of a molecule, comprising:

[0007] Acquire a conformation sequence of a molecule and mechanical perturbation data of the molecule; the conformation sequence includes a plurality of initial conformations of the molecule; the plurality of initial conformations correspond one to one with moments in a preset time sequence; each initial conformation is used to characterize the spatial position of each atom in the molecule at a corresponding moment; each initial conformation has a corresponding initial force value;

[0008] According to the selection of the target moment in the time series, a first initial conformation and a second initial conformation in the conformation sequence are determined; the first initial conformation corresponds to the target moment, and the second initial conformation corresponds to a moment before the target moment;

[0009] Applying the mechanical perturbation data to the first initial conformation of the molecule to obtain a perturbed conformation of the molecule at the target time;

[0010] Using the first initial conformation and the second initial conformation as sampling data of a local Gaussian distribution, determining the variance of the local Gaussian distribution, and determining the steady-state conformation of the molecule at the target time;

[0011] The conservative force exerted on the perturbed conformation of the molecule at the target moment is determined based on the variance, the perturbed conformation, and the steady-state conformation.

[0012] In a second aspect, the present application also discloses a device for determining the force of disturbing the molecular conformation, comprising:

[0013] A sequence acquisition module, used to acquire a conformation sequence of a molecule and mechanical perturbation data of the molecule; the conformation sequence includes a plurality of initial conformations of the molecule; the plurality of initial conformations correspond one to one with moments in a preset time sequence; each initial conformation is used to characterize the spatial position of each atom in the molecule at a corresponding moment; each initial conformation has a corresponding initial force value;

[0014] A sequence extraction module, for determining a first initial conformation and a second initial conformation in the conformation sequence according to the selection of a target moment in the time sequence; the first initial conformation corresponds to the target moment, and the second initial conformation corresponds to a moment before the target moment;

[0015] A perturbation generating module, used for applying the mechanical perturbation data to the first initial conformation of the molecule to obtain a perturbed conformation of the molecule at the target time;

[0016] a distribution construction module, configured to use the first initial conformation and the second initial conformation as sampling data of a local Gaussian distribution, determine the variance of the local Gaussian distribution, and determine the steady-state conformation of the molecule at the target time;

[0017] The force calculation module is used to determine the conservative force exerted on the disturbed conformation of the molecule at the target moment according to the variance, the disturbed conformation, and the steady-state conformation.

[0018] In a third aspect, an embodiment of the present application further discloses an electronic device, comprising a processor and a memory, wherein the memory stores programs or instructions that can be run on the processor, and when the program or instructions are executed by the processor, the steps of the method described in the first aspect are implemented.

[0019] In a fourth aspect, an embodiment of the present application further discloses a readable storage medium, on which a program or instruction is stored. When the program or instruction is executed by a processor, the steps of the method described in the first aspect are implemented.

[0020] In summary, in the embodiment of the present application, by applying mechanical perturbation data to the first initial conformation, the perturbation that the molecule may encounter in the actual environment is determined, thereby obtaining the conformational behavior of the molecule under external force perturbation, and starting from the property of the local Gaussian distribution obeyed between the initial conformations at two adjacent moments, the first initial conformation and the second initial conformation are determined in the conformation sequence, and the two are used as sampling data of the local Gaussian distribution to determine the relevant parameters of the local Gaussian distribution, and finally the conservative force received by the perturbed conformation is reversed according to the relevant parameters, thereby bypassing the step-by-step analysis of complex data and reducing the dependence on parameter adjustment and basic data selection. Thus, based on the method of the embodiment of the present application, in the process of determining the force of the molecule, there is no need to rely on complex basic data and the huge computing power relied on by the large-scale deep model, and the final result can be obtained, which solves the problem of the complexity of obtaining the data basis and the high computing power requirements of the computing equipment in the molecular dynamics simulation in the calculation process of the force. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In the attached picture:

[0022] Figure 1 is a flowchart of the steps of a method for determining the force of disturbing the molecular conformation provided in an embodiment of the present application;

[0023] Figure 2 is a flowchart of the steps of another method for determining the force of disturbing the molecular conformation provided by an embodiment of the present application;

[0024] Figure 3 is a flow chart of a calculation process of another method for determining the force of disturbing molecular conformation provided in an embodiment of the present application;

[0025] Figure 4 is a block diagram of a device for determining a force perturbing a molecular conformation provided in an embodiment of the present application;

[0026] Figure 5 is a block diagram of an electronic device according to an embodiment of the present application;

[0027] Figure 6 It is a block diagram of an electronic device of another embodiment provided by the embodiments of the present application. DETAILED DESCRIPTION

[0028] 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 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.

[0029] The terms "first", "second", etc. in this application are used to distinguish similar objects, and are not used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable under appropriate circumstances, so that the embodiments of the present application can be implemented in an order other than those illustrated or described here, and the objects distinguished by "first", "second", etc. are usually a class, and the number of objects is not limited. For example, the first object can be one or more. In addition, in this application, "and / or" represents at least one of the connected objects, and the character " / " generally indicates that the objects associated with each other are in an "or" relationship.

[0030] In the process of solving the forces on molecules, the molecule can be regarded as an atomic system. Different conformations of the same molecule correspond to different atoms in different conformations in different spatial positions, and the energy of molecules with different structures is also different. The probability of a molecule being in a certain conformation follows the Boltzmann distribution:

[0031] ;

[0032] The matrix X represents the molecular conformation, that is, each row of the matrix corresponds to the coordinates of an atom, E is the energy of the molecule in this conformation, k represents the Boltzmann constant, T is the temperature, Z is the normalization constant, and p(X) is the probability in this conformation. By taking the logarithm and calculating the gradient of the atomic coordinate X, since the negative energy derivative corresponds to the force, the relationship between the force F on the atom can be obtained: , where F is defined as If the above negative gradient is regarded as an approximate pseudo force, the objective function of a machine learning force field model can be obtained:

[0033] ;

[0034] in, is a machine learning force field model, is the force field model's estimate of the force on conformation X, represents the objective function, It means to find the gradient of X. The Frobenius norm is calculated as the difference between the estimated value and the true value, and E[·] is the mathematical expectation operator.

[0035] Based on the above definition, from the perspective of statistical physics, the molecular conformation X (X∈R n×3 ) can be viewed as a function of the Boltzmann distribution p(X) (p(X)∝e -E(X) ), where E(X) is the energy of X, and R n×3 It represents an n×3 dimensional matrix space in the real number domain, where n is the number of atoms in the molecule being analyzed.

[0036] Then, from the distribution p(X), we can see that the probability of occurrence of low-energy structures is very high. When there is a set of molecular equilibrium conformations X1,…,X n (Here we can assume that its energy is locally minimum), where X1,…,X n are the local maxima of the distribution p(X) respectively. Sampling a perturbed sample from the local distribution centered at the equilibrium conformation X , replace p(X) with a mixed Gaussian approximation centered at the equilibrium conformation:

[0037] ;

[0038] At this time, define , indicating that X i is the mean, is a Gaussian distribution with variance yes The variance of the distribution, is the identity matrix of N rows and 3 columns, X i is the ith equilibrium conformation, then this approximation shows that will have a local maximum at the equilibrium conformation. Substitute into the objective function equation, and according to , then the learning force field can approximate the objective function as Expectation under the distribution:

[0039] ;

[0040] Since the molecule always approaches the steady state during the dynamics simulation, the molecular conformation at any time in the molecular trajectory and its adjacent time is always distributed near a certain equilibrium conformation, which we call the local steady-state point. Therefore, in theory, there is a set of equilibrium conformations X1,…,X n Therefore, the above-mentioned Gaussian mixture approximation method can be used, assuming that a certain local equilibrium conformation is X0, and the molecular conformation in the local distribution is X, Then add a perturbation to X Get the perturbed conformation , (at this time, control is required The size of is such that the perturbed conformations are still distributed in this local Gaussian distribution).

[0041] So there is, ,and The distribution function of is:

[0042] ;

[0043] Now we can bring in the objective function and get:

[0044] ;

[0045] According to the second term on the right side of the above formula, we can get:

[0046] ;

[0047] Therefore, the logarithmic distribution of the perturbed conformations can be expressed relative to Gradient approximation The force is:

[0048] ,

[0049] Where d represents the dimension of X, that is, in the above formula: d=3n.

[0050] Based on the derivation of the above process, Figure 1 As shown, a method for determining the force of disturbing the molecular conformation provided by this embodiment is obtained, and the method may include the following steps:

[0051] Step 101, obtaining the conformational sequence of the molecule and the mechanical perturbation data of the molecule.

[0052] Among them, the conformation sequence includes multiple initial conformations of the molecule; the multiple initial conformations correspond one-to-one to the moments in the preset time series; each initial conformation is used to characterize the spatial position of each atom in the molecule at the corresponding moment; and each initial conformation has a corresponding initial force value.

[0053] In some embodiments of the present application, a process of obtaining a conformational sequence of a molecule and its mechanical perturbation data is performed. A conformational sequence refers to a collection of spatial structures of a molecule at different time points, and each conformation represents the three-dimensional spatial arrangement of the molecule at a specific moment. These conformations correspond to moments in the time series, and each conformation has its corresponding atomic force. In this step, it is first necessary to determine the time series of the molecular sample, and then collect the molecular conformation and corresponding atomic force data at each time point.

[0054] For example, consider a simulation system containing several water molecules. At the beginning of the simulation, the initial conformation and atomic forces of each water molecule are recorded, and these data constitute part of the conformational sequence. As the simulation proceeds, the conformations and forces of all water molecules are recorded again at regular time intervals until the end of the simulation. In this way, a complete conformational sequence is obtained, which contains the conformational and force data of all water molecules from the beginning to the end of the simulation. These data can be used for subsequent analysis, such as calculating the changes in forces when the molecules are subjected to external perturbations. In this example, the conformational sequence provides detailed information on the molecular dynamics trajectory and provides basic data for the implementation of subsequent steps.

[0055] Step 102: Determine a first initial conformation and a second initial conformation in the conformation sequence according to the selection of the target moment in the time sequence.

[0056] The first initial conformation corresponds to the target moment, and the second initial conformation corresponds to the moment before the target moment.

[0057] In some embodiments of the present application, it is necessary to determine the first initial conformation and the second initial conformation at the target moment in the time sequence. The first initial conformation refers to the spatial structure of the molecule at the target moment, while the second initial conformation is the spatial structure of the molecule at the moment before the target moment. The key to this step is to extract the molecular conformation corresponding to the moment and the moment before it from the conformation sequence. These conformations will be used for mechanical perturbation data analysis and determination of steady-state conformations in subsequent steps.

[0058] For example, suppose there are 500 consecutive picosecond moments in a molecular dynamics simulation, and suppose the target moment is selected as the 100th picosecond of the simulation time. Then at this moment, the conformation of the molecule (the first initial conformation) and the conformation of the previous moment, i.e., the 99th picosecond (the second initial conformation) will be recorded. These two conformations will serve as the basic data for analyzing the force changes of the molecule in the subsequent steps. In this example, the first initial conformation and the second initial conformation provide detailed spatial arrangement information of the molecule at a specific moment and the moment before it, providing the necessary input data for the implementation of the subsequent steps.

[0059] Step 103, applying the mechanical perturbation data to the first initial conformation of the molecule to obtain the perturbed conformation of the molecule at the target time.

[0060] In some embodiments of the present application, mechanical perturbation data is applied to the first initial conformation of the molecule to obtain a perturbed conformation at the target moment. Mechanical perturbation data refers to a series of external factors applied to the molecular conformation, such as temperature changes, pressure changes, or other chemical reactions, which can cause the molecular conformation to change. In this step, by simulating these perturbations, it is possible to predict conformational changes of the molecule under external influences that may be encountered in the actual environment.

[0061] For example, assuming that the first initial conformation of a molecular conformation at the target time is known, a small perturbation can be applied to it according to actual needs. The perturbation can be random or preset according to the purpose of the experiment. This can be achieved by adding a small vector to each atomic coordinate of the molecular conformation, which represents the increment of atomic motion. After the perturbation is applied, the new conformation obtained is the perturbed conformation. In this example, the perturbed conformation reflects the new state of the molecule after being subjected to external perturbations, and provides simulation results as a data basis for the implementation of subsequent steps.

[0062] Step 104 , using the first initial conformation and the second initial conformation as sampling data of the local Gaussian distribution, determining the variance of the local Gaussian distribution, and determining the steady-state conformation of the molecule at the target time.

[0063] In some embodiments of the present application, the first initial conformation and the second initial conformation are used as sampling data of the local Gaussian distribution to determine the variance of the distribution. In addition, this step also involves determining the steady-state conformation of the molecule at the target time. The local Gaussian distribution refers to the statistical distribution of the molecular conformation when the local energy is minimized, and its variance reflects the fluctuation size of the molecular conformation near the steady state. By analyzing the conformation at two consecutive moments as sampling data, the steady state and variance of the molecular conformation can be estimated.

[0064] For example, suppose that in a molecular dynamics simulation, the first initial conformation at a certain target moment and the second initial conformation at the previous moment have been obtained. These two conformations can be regarded as samples drawn from a local Gaussian distribution. By calculating the coordinate difference between the two conformations, the variance of the local Gaussian distribution can be estimated. Further, using this variance and the information of the two conformations, the steady-state conformation of the molecule at the target moment can be determined. In this example, the steady-state conformation represents the most likely conformation of the molecule when it is not subjected to external perturbations, while the variance provides information about the size of the molecular conformational fluctuations, which will provide a quantitative analytical basis for the subsequent steps to solve the conservative forces acting on the perturbed conformation.

[0065] Step 105, determining the conservative force on the perturbed conformation of the molecule at the target time according to the variance, the perturbed conformation, and the steady-state conformation.

[0066] In some embodiments of the present application, the conservative force to which the perturbed conformation of the molecule at the target time is subjected is determined based on the variance, the perturbed conformation, and the steady-state conformation. The key to this step is to use the known variance and steady-state conformation, combined with the perturbed conformation, to calculate the conservative force, which is a process of estimating based on statistical distribution and a small number of sampling points. This can predict the mechanical response of the molecule when it is subjected to external perturbations in the actual environment.

[0067] For example, suppose the perturbed conformation and steady-state conformation of a molecule at a target time are known, as well as the variance obtained from the previous step. Then, the difference between the perturbed conformation and the steady-state conformation can be calculated first, and then the variance can be used to adjust this difference to obtain an estimate of the force on the perturbed conformation. Based on the derivation process explained earlier, this estimate will be equivalent to the result predicted by the deep model, that is, the two have the same effect under the premise of reducing data complexity and computational complexity.

[0068] In summary, in the embodiment of the present application, by applying mechanical perturbation data to the first initial conformation, the perturbation that the molecule may encounter in the actual environment is determined, thereby obtaining the conformational behavior of the molecule under external force perturbation, and starting from the property of the local Gaussian distribution obeyed between the initial conformations at two adjacent moments, the first initial conformation and the second initial conformation are determined in the conformation sequence, and the two are used as sampling data of the local Gaussian distribution to determine the relevant parameters of the local Gaussian distribution, and finally the conservative force received by the perturbed conformation is reversed according to the relevant parameters, thereby bypassing the step-by-step analysis of complex data and reducing the dependence on parameter adjustment and basic data selection. Thus, based on the method of the embodiment of the present application, in the process of determining the force of the molecule, there is no need to rely on complex basic data and the huge computing power relied on by the large-scale deep model, and the final result can be obtained, which solves the problem of the complexity of obtaining the data basis and the high computing power requirements of the computing equipment in the molecular dynamics simulation in the calculation process of the force.

[0069] Figure 2 Another method for determining the force of disturbing the molecular conformation provided in the application embodiment is as follows: Figure 2 , the method may include the following steps:

[0070] Step 201, obtaining the conformational sequence of the molecule and the mechanical perturbation data of the molecule.

[0071] Among them, the conformation sequence includes multiple initial conformations of the molecule; the multiple initial conformations correspond one-to-one to the moments in the preset time series; each initial conformation is used to characterize the spatial position of each atom in the molecule at the corresponding moment; and each initial conformation has a corresponding initial force value.

[0072] The method shown in this step has been explained in step 101 and will not be repeated here.

[0073] Step 202: Determine a first initial conformation and a second initial conformation in the conformation sequence according to the selection of the target moment in the time sequence.

[0074] The first initial conformation corresponds to the target moment, and the second initial conformation corresponds to the moment before the target moment.

[0075] The method shown in this step has been explained in step 102 and will not be repeated here.

[0076] Step 203, applying the mechanical perturbation data to the first initial conformation of the molecule to obtain the perturbed conformation of the molecule at the target time.

[0077] The method shown in this step has been explained in step 103 and will not be repeated here.

[0078] Optionally, the mechanical perturbation data records the perturbation value corresponding to each atom in the molecule, the first initial conformation includes the spatial coordinates corresponding to each atom in the molecule, and step 203 includes the following sub-steps:

[0079] Sub-step 2031, taking the sum of the disturbance value corresponding to the atom in the disturbance value and the spatial coordinate as the spatial coordinate of the atom in the molecule at the target time.

[0080] In some embodiments of the present application, this step is used to determine the atomic spatial coordinates of a molecule at a target time. The mechanical perturbation data value refers to the change in the atomic position caused by changes in external conditions (such as temperature, pressure, or chemical reaction). In this step, the perturbation value of each atom is added to its spatial coordinates in the first initial conformation to obtain the perturbed conformation of the molecule at the target time: Assuming that at time t1, the first initial conformation of the molecule is X1, the mechanical perturbation data is , then the perturbed conformation at this time That is, according to the formula Obtained by calculation.

[0081] For example, suppose that in a molecular dynamics simulation, the spatial coordinates of the oxygen atom of a water molecule in the initial conformation are (0,1,0). Due to thermal perturbations, the position of the oxygen atom changes slightly, and the perturbation value is (0.01, -0.01, 0.02). Then the perturbation value can be added to the spatial coordinates to obtain the new spatial coordinates of the oxygen atom at the target time (0.01, 0.99,0.02). By performing the same operation on all atoms in the water molecule, the perturbed conformation of the entire molecule at the target time can be obtained. This process provides an intuitive way to understand the behavior of molecules when subjected to external perturbations.

[0082] Step 204 , using the first initial conformation and the second initial conformation as sampling data of the local Gaussian distribution, determining the variance of the local Gaussian distribution, and determining the steady-state conformation of the molecule at the target time.

[0083] The method shown in this step has been explained in step 104 and will not be repeated here.

[0084] Optionally, in order to use the first initial conformation and the second initial conformation as sampling data of the local Gaussian distribution and determine the variance of the local Gaussian distribution, step 204 includes the following sub-steps:

[0085] Sub-step 2041, determining the force matrix of the molecule at the target time according to the first initial force value corresponding to the first initial conformation and the second initial force value corresponding to the second initial conformation.

[0086] In some embodiments of the present application, the force matrix of the molecule at the target time is determined. The force matrix is ​​a mathematical expression that contains the magnitude and direction of the force to which each atom in the molecule is subjected at the target time. This step requires the use of data of the first initial force value and the second initial force value, which reflect the force conditions of the molecule at two consecutive moments. By comparing the forces at these two moments, the force matrix of the molecule at the target moment can be estimated.

[0087] For example, suppose in a molecular dynamics simulation, the forces on a molecule at time t1 and t2 are F1 and F2 respectively. These two forces can be expressed in matrix form, where each row represents an atom and each column represents a force in a spatial dimension. By calculating the difference between these two matrices, the force matrix F2-F1 at the target time t2 can be obtained. This force matrix will be used to calculate the energy matrix in the subsequent steps. In this example, the force matrix provides detailed information on the force state of the molecule at the target time, providing a quantitative basis for the implementation of the subsequent steps.

[0088] Sub-step 2042, determining the energy matrix of the molecule at the target time according to the first initial conformation, the second initial conformation and the force matrix.

[0089] In some embodiments of the present application, the energy matrix of the molecule at the target time is determined. The energy matrix is ​​a mathematical expression that contains the energy value of each atom in the molecule at a specific conformation. The key to this step is to combine the conformation of the molecule at two consecutive times with the force matrix and calculate the energy state of the molecule at the target time.

[0090] For example, suppose that in a molecular dynamics simulation, the conformation of a molecule at time t1 is X1, and the conformation at time t2 is X2, and the force matrices F1 and F2 at these two times are known. By calculating the difference between X2 and X1, and the difference between F2 and F1, the energy matrix can be obtained. The specific calculation method involves combining the conformational differences with the force differences to estimate the energy changes. In this example, the energy matrix provides detailed information about the energy state of the molecule at the target time, providing a quantitative basis for the implementation of subsequent steps.

[0091] Optionally, sub-step 2042 includes the following sub-steps:

[0092] Sub-step 20421, determining the conformational variable matrix of the molecule according to the first initial conformation and the second initial conformation.

[0093] In some embodiments of the present application, in this embodiment, the conformational variable matrix of the molecule is determined based on the first initial conformation and the second initial conformation. The conformational variable matrix is ​​a mathematical expression that contains the amount of change between the conformations of the molecule at two consecutive moments. The purpose of this step is to obtain the change information of the molecular conformation by analyzing the conformational differences at two moments, which is essential for the subsequent calculation of the energy matrix and variance.

[0094] For example, suppose that in a molecular dynamics simulation, a molecule has a conformation X1 at time t1 and a conformation X2 at time t2. The conformational variable matrix △X can be determined by calculating the difference between X2 and X1, that is: In this example, the conformational variable matrix △X provides the conformational change of the molecule from time t1 to t2, providing a quantitative basis for the implementation of subsequent steps.

[0095] Sub-step 20422, multiply the conformational variable matrix and the force matrix bit by bit to obtain the energy matrix.

[0096] In some embodiments of the present application, in this embodiment, the energy matrix is ​​obtained by performing a bitwise product operation on the conformational variable matrix and the force matrix. The energy matrix is ​​a mathematical expression that contains the energy values ​​of the molecule in a specific conformation. Bitwise product refers to multiplication of the elements in the same position of the two matrices. The purpose of this step is to calculate the energy state of the molecule at the target time by combining the change in the molecular conformation and the corresponding force.

[0097] For example, suppose that in a molecular dynamics simulation, the conformational variable matrix △X and the force matrix F are obtained. Then the energy matrix E can be obtained by the formula E=ΔX⊙F, where the ⊙ symbol represents the bitwise product operation. In this example, the energy matrix E provides detailed information about the energy state of the molecule at the target moment, providing a quantitative basis for the implementation of subsequent steps. In this way, the energy change of the molecule when it is perturbed can be more accurately estimated.

[0098] Sub-step 2043, taking the ratio of the sum of all non-negative components of the energy matrix to the sum of squares of the corresponding components in the force matrix as the variance of the local Gaussian distribution.

[0099] In some embodiments of the present application, the ratio of the sum of all non-negative components of the energy matrix to the sum of the squares of the corresponding components is calculated as the variance of the local Gaussian distribution. Variance is a measure of the degree of discreteness of a random variable or a set of data in statistics. In molecular dynamics, variance can be used to describe the fluctuation range of molecular conformations near the steady state. The key to this step is to combine the energy matrix with the force matrix and determine the variance of the local Gaussian distribution by their ratio.

[0100] For example, suppose that in a molecular dynamics simulation, the energy matrix E and force matrix F of the molecule at the target time have been calculated. The sum of all non-negative components of the energy matrix E is expressed as ∑E i ,(E i >0), the sum of the squares of all corresponding components of the force matrix F is expressed as ∑F i 2 ,(E i >0). The variance σ of the local Gaussian distribution 2 The formula σ 2 =∑E i / ∑F i 2 ,(E i >0). In this example, by calculating the relevant values ​​of the energy matrix and the force matrix, the variance of the local Gaussian distribution can be obtained, which provides quantitative results for the implementation of subsequent steps and can be used to analyze the behavior of molecules when they are disturbed.

[0101] Optionally, in order to determine the steady-state conformation of the molecule at the target time, step 204 includes the following sub-steps:

[0102] Sub-step 2044, determining the average conformation of the molecule based on the first initial conformation and the second initial conformation.

[0103] In some embodiments of the present application, the average conformation of the molecule is determined by calculating the average of the first initial conformation and the second initial conformation. The average conformation refers to the average spatial position of the molecular conformation at two consecutive moments, which can reflect the average state of the molecule between the two moments. This step is very important for estimating the steady-state conformation of the molecule at the target moment, because the steady-state conformation usually corresponds to the average conformation of the molecule over a period of time.

[0104] For example, suppose in a molecular dynamics simulation, a molecule has a conformation X1 at time t1 and a conformation X2 at time t2. The average conformation X bar The formula X bar =(X1+X2) / 2. In this example, the conformational average X bar The average spatial position of the molecule at time t1 and t2 is provided, providing a quantitative basis for the implementation of subsequent steps. This calculation method can be applied to any number of atoms and molecular types, providing a simple and effective method for determining the steady-state conformation of a molecule.

[0105] Sub-step 2045, determining the average force value of the molecule according to the first initial force value corresponding to the first initial conformation and the second initial force value corresponding to the second initial conformation.

[0106] In some embodiments of the present application, the average of the first initial force value corresponding to the first initial conformation and the second initial force value corresponding to the second initial conformation is calculated to determine the average force value of the molecule. The average force value refers to the average force condition of the molecule at two consecutive moments, which helps to estimate the average force state of the molecule during this period. This step is very important for understanding the steady-state behavior of the molecule at the target moment.

[0107] For example, suppose in a molecular dynamics simulation, the forces on a molecule at time t1 and t2 are F1 and F2 respectively. The average force F bar The formula F bar =(F1+F2) / 2. In this example, the average force F bar The average force on the molecule at t1 and t2 is provided, providing a quantitative basis for the implementation of subsequent steps. This calculation method can be applied to any number of atoms and molecule types, providing a simple and effective method for determining the steady-state force on the molecule.

[0108] Sub-step 2046, the product of the force average value and the variance and the sum of the conformation average value are determined as the steady-state conformation.

[0109] In some embodiments of the present application, the product of the force average and the variance, and the conformation average, are combined to determine the steady-state conformation of the molecule. The steady-state conformation refers to the conformation that the molecule is most likely to take when it is at its lowest energy point, which is an important concept in molecular dynamics research. The key to this step is to use the known force average and variance, as well as the conformation average, to estimate the conformation of the molecule in the steady state.

[0110] For example, suppose that in the molecular dynamics simulation, the average force F bar , the conformational average value X bar , and the variance σ is known 2 The steady-state conformation X0 can be expressed by the formula Calculated. In this example, the steady-state conformation X0 provides the expected conformation of the molecule at the lowest energy, providing a quantitative basis for the implementation of subsequent steps. This calculation method can be applied to any number of atoms and molecular types, providing a simple and effective method for determining the steady-state conformation of a molecule.

[0111] Step 205, determining the conservative force on the perturbed conformation of the molecule at the target time according to the variance, the perturbed conformation, and the steady-state conformation.

[0112] The method shown in this step has been explained in step 105 and will not be repeated here.

[0113] Optionally, step 205 includes the following sub-steps:

[0114] Sub-step 2051, determining the average force value of the molecule according to the first initial force value corresponding to the first initial conformation and the second initial force value corresponding to the second initial conformation.

[0115] The method shown in this step has been explained in sub-step 2045 and will not be repeated here.

[0116] Sub-step 2052, determining a first conformational difference of the molecule according to the difference between the first initial conformation and the steady-state conformation, and determining a second conformational difference of the molecule according to the difference between the steady-state conformation and the second initial conformation.

[0117] In some embodiments of the present application, the first conformational difference and the second conformational difference of the molecule are calculated. The first conformational difference refers to the difference between the first initial conformation and the steady-state conformation, while the second conformational difference refers to the difference between the steady-state conformation and the second initial conformation. These conformational differences help understand the conformational changes of the molecule from one moment to another, and how the molecule approaches or moves away from the steady-state conformation.

[0118] For example, suppose in a molecular dynamics simulation, the conformation of a molecule at time t1 is X1, the conformation at time t2 is X2, and the steady-state conformation is known to be X0. Then the first conformation difference △1X and the second conformation difference △2X can be calculated by the following formula: , In this example, the first conformational difference and the second conformational difference provide the amount of spatial position change between the molecule and the steady-state conformation at two consecutive moments, providing a quantitative basis for the implementation of subsequent steps. This calculation method can be applied to any number of atoms and molecular types, providing a simple and effective method for analyzing the dynamic behavior and steady-state proximity of molecules.

[0119] Sub-step 2053, determining the ratio of the average value of the first conformational difference and the second conformational difference to the variance as the third conformational difference of the molecule.

[0120] In some embodiments of the present application, in this embodiment, the average value of the first conformational difference and the second conformational difference is calculated and combined with the ratio of the variance to determine the third conformational difference of the molecule. The third conformational difference is a measure of the change of the molecule from the initial state to the steady state, which reflects the overall trend of the molecular conformational change.

[0121] For example, suppose that in the molecular dynamics simulation, the first conformational difference Δ1X and the second conformational difference Δ2X have been obtained, as well as the variance σ obtained from the previous step 2 Then the third conformational difference Δ3X can be expressed by the formula Calculated. In this example, the third conformational difference Δ3X provides a quantitative measure that indicates the average conformational change of the molecule as it approaches steady state, providing a quantitative basis for the implementation of subsequent steps. This computational method helps predict the behavior of molecules when perturbed, which is very important for understanding molecular dynamics and conducting related scientific research.

[0122] Sub-step 2054, the sum of the average force and the third conformational difference is determined as the conservative force on the perturbed conformation of the molecule.

[0123] In some embodiments of the present application, the force average value is finally combined with the sum of the third conformational differences to determine the conservative force on the perturbed conformation of the molecule. The purpose of this step is to estimate the force state of the molecule when it is perturbed by combining the quantitative information of the force average value and the conformational differences.

[0124] For example, suppose that in the molecular dynamics simulation, the average force F bar , and the third conformational difference Δ3X is obtained. Then the conservative force F on the opposing conformation is ϵ The formula can be In this example, the conservative force It provides the expected stress state of the molecule after being disturbed, providing a quantitative basis for the implementation of subsequent steps. This computational method helps to predict the mechanical response of molecules under disturbances that they may encounter in actual environments, which is very important for understanding the dynamic behavior of molecules and conducting related scientific research.

[0125] According to the process from sub-step 2051 to sub-step 2054, it is not difficult to see that the conservative force can also be directly derived by the following formula :

[0126] .

[0127] Optionally, when there are multiple molecules, the present application further includes steps 206 and 207:

[0128] Step 206, determining the perturbed conformation of each molecule and the conservative force exerted on each perturbed conformation according to the conformation sequences corresponding to the multiple molecules.

[0129] In some embodiments of the present application, in a system with multiple molecules, the perturbed conformation of each molecule after being subjected to mechanical perturbation data and the corresponding conservative force it is subjected to are determined separately according to the conformation sequence corresponding to each molecule. This step is carried out in a multi-molecule system, and is intended to estimate the force conditions under a specific perturbation for each molecule individually. This requires analyzing the conformation sequence of each molecule to determine its new conformation and the changes in atomic force when subjected to external perturbations.

[0130] For example, suppose a simulation system contains multiple types of molecules, including multiple water molecules. Then, the conformational sequence of each molecule during the simulation can be collected first. Then, the same or different mechanical perturbation data is applied to each type of molecule, such as simulating thermal perturbations by increasing the temperature. For each type of molecule, the new conformation after the perturbation and the changes in atomic forces are recorded. In this way, the perturbed conformation of each molecule under a specific perturbation and the conservative forces it is subjected to can be obtained, providing basic data for further data analysis and model training. In this example, the determination of the perturbed conformation of each molecule and the conservative forces it is subjected to are carried out independently, ensuring the accuracy and reliability of the force prediction of each molecule in the multi-molecule system.

[0131] Step 207, generating a perturbed conformation data set of the molecule according to the determined multiple perturbed conformations and the conservation forces corresponding to the perturbed conformations.

[0132] In some embodiments of the present application, a molecular perturbation conformation data set containing these data will be generated based on the determined multiple perturbed conformations and the corresponding conservative forces they are subjected to. This data set will contain the new conformation of each molecule after being subjected to a specific perturbation and the corresponding force information, which is essential for understanding the behavior of molecules under different conditions and conducting further scientific research.

[0133] For example, consider a simulation system containing multiple molecules, such as protein molecules. For each molecule, the perturbed conformations after thermal perturbation and the conservation forces to which the perturbed conformations are subjected have been determined. This information is aggregated to form a dataset containing all perturbed conformations and the corresponding conservation forces for each molecule type. This dataset can be used to train a machine learning model to predict the behavior of molecules under different perturbation conditions that they may encounter in the future. In this example, the perturbed conformation dataset provides a valuable resource for molecular dynamics and force field studies, which can be used in a variety of scientific and engineering applications, such as drug design and materials science.

[0134] like Figure 3 FIG. 1 is a flowchart of a calculation process of another method for determining the force of disturbing the molecular conformation provided in an embodiment of the present application:

[0135] Step S1: Select time t in the time series n The corresponding molecular conformation X n and the atomic force F n , and the previous moment t n-1 The corresponding molecular conformation X n-1 and the atomic force F n-1 Step S1 serves as a preparatory step to provide necessary data for subsequent perturbation analysis and determination of steady-state conformation.

[0136] Step S2: For molecular conformation X n Add perturbation to obtain the perturbed conformation This step simulates the conformational changes of the molecule when it is subjected to external influences, providing a basis for calculating the conservative forces acting on the perturbed conformation.

[0137] Step S3: Calculate time t n The local steady-state conformation X0 and variance σ 2 The local stable conformation represents the lowest energy state of the molecule, while the variance describes the fluctuation range of the molecular conformation around the stable state.

[0138] Step S4: Calculate the perturbed conformation Atomic forces This is the final step, in which the data from the previous steps are used to estimate the forces acting on the molecule in the perturbed conformation.

[0139] In summary, in the embodiment of the present application, by applying mechanical perturbation data to the first initial conformation, the perturbation that the molecule may encounter in the actual environment is determined, thereby obtaining the conformational behavior of the molecule under external force perturbation, and starting from the property of the local Gaussian distribution obeyed between the initial conformations at two adjacent moments, the first initial conformation and the second initial conformation are determined in the conformation sequence, and the two are used as sampling data of the local Gaussian distribution to determine the relevant parameters of the local Gaussian distribution, and finally the conservative force received by the perturbed conformation is reversed according to the relevant parameters, thereby bypassing the step-by-step analysis of complex data and reducing the dependence on parameter adjustment and basic data selection. Thus, based on the method of the embodiment of the present application, in the process of determining the force of the molecule, there is no need to rely on complex basic data and the huge computing power relied on by the large-scale deep model, and the final result can be obtained, which solves the problem of the complexity of obtaining the data basis and the high computing power requirements of the computing equipment in the molecular dynamics simulation in the calculation process of the force.

[0140] refer to Figure 4 , which shows a device 30 for determining the force of disturbing the molecular conformation provided by an embodiment of the present application, comprising:

[0141] The sequence acquisition module 301 is used to acquire the conformation sequence of the molecule and the mechanical perturbation data of the molecule; the conformation sequence includes multiple initial conformations of the molecule; the multiple initial conformations correspond to the moments in the preset time sequence one by one; each initial conformation is used to represent the spatial position of each atom in the molecule at the corresponding moment; each initial conformation has a corresponding initial force value;

[0142] The sequence extraction module 302 is used to determine the first initial conformation and the second initial conformation in the conformation sequence according to the selection of the target moment in the time sequence; the first initial conformation corresponds to the target moment, and the second initial conformation corresponds to the moment before the target moment;

[0143] A perturbation generation module 303, for applying mechanical perturbation data to the first initial conformation of the molecule to obtain a perturbed conformation of the molecule at a target time;

[0144] A distribution construction module 304 is used to use the first initial conformation and the second initial conformation as sampling data of the local Gaussian distribution, determine the variance of the local Gaussian distribution, and determine the steady-state conformation of the molecule at the target time;

[0145] The force calculation module 305 is used to determine the conservative force exerted on the disturbed conformation of the molecule at the target time according to the variance, the disturbed conformation, and the steady-state conformation.

[0146] Optionally, the mechanical perturbation data records a perturbation value corresponding to each atom in the molecule, the first initial conformation includes a spatial coordinate corresponding to each atom in the molecule, and the perturbation generation module 303 includes:

[0147] The perturbation generation submodule is used to take the sum of the perturbation value of the corresponding atom in the perturbation value and the spatial coordinate as the spatial coordinate of the atom of the molecule at the target time.

[0148] Optionally, the distribution construction module 304 includes:

[0149] A force matrix submodule, used to determine the force matrix of the molecule at a target time according to a first initial force value corresponding to the first initial conformation and a second initial force value corresponding to the second initial conformation;

[0150] An energy matrix submodule, used to determine the energy matrix of the molecule at a target time according to the first initial conformation, the second initial conformation and the force matrix;

[0151] The variance submodule is used to calculate the ratio of the sum of all non-negative components of the energy matrix to the sum of squares of the corresponding components in the force matrix.

[0152] Optionally, the energy matrix submodule includes:

[0153] A conformation variable unit, used for determining a conformation variable matrix of the molecule according to the first initial conformation and the second initial conformation;

[0154] The energy matrix unit is used to obtain the energy matrix by taking the bitwise product of the conformational variable matrix and the force matrix.

[0155] Optionally, the distribution construction module 304 includes:

[0156] A conformation average submodule, used for determining the conformation average of the molecule according to the first initial conformation and the second initial conformation;

[0157] A force average submodule, used to determine an average force value of the molecule according to a first initial force value corresponding to the first initial conformation and a second initial force value corresponding to the second initial conformation;

[0158] The steady-state conformation submodule is used to determine the steady-state conformation by taking the product of the force average value and the variance and the sum of the conformation average value.

[0159] Optionally, the force calculation module 305 includes:

[0160] A force average value submodule, used to determine the force average value of the molecule according to a first initial force value corresponding to the first initial conformation and a second initial force value corresponding to the second initial conformation;

[0161] A conformational difference pre-calculation submodule, for determining a first conformational difference of the molecule according to a difference between the first initial conformation and the steady-state conformation, and determining a second conformational difference of the molecule according to a difference between the steady-state conformation and the second initial conformation;

[0162] A conformational difference calculation submodule, used for determining the ratio of the average value of the first conformational difference and the second conformational difference to the variance as the third conformational difference of the molecule;

[0163] The perturbed conformation force submodule is used to determine the sum of the average force and the third conformation difference as the conservative force on the perturbed conformation of the molecule.

[0164] Optionally, there are multiple molecules, and the device 30 for determining the force that disturbs the molecular conformation further includes:

[0165] A traversal module is used to determine the perturbed conformation of each molecule and the conservative force exerted on each perturbed conformation according to the conformational sequences corresponding to multiple molecules;

[0166] The data set module is used to generate a perturbed conformation data set of a molecule according to a plurality of determined perturbed conformations and conservation forces corresponding to the perturbed conformations.

[0167] In summary, in the embodiment of the present application, by applying mechanical perturbation data to the first initial conformation, the perturbation that the molecule may encounter in the actual environment is determined, thereby obtaining the conformational behavior of the molecule under external force perturbation, and starting from the property of the local Gaussian distribution obeyed between the initial conformations at two adjacent moments, the first initial conformation and the second initial conformation are determined in the conformation sequence, and the two are used as sampling data of the local Gaussian distribution to determine the relevant parameters of the local Gaussian distribution, and finally the conservative force received by the perturbed conformation is reversed according to the relevant parameters, thereby bypassing the step-by-step analysis of complex data and reducing the dependence on parameter adjustment and basic data selection. Thus, based on the method of the embodiment of the present application, in the process of determining the force of the molecule, there is no need to rely on complex basic data and the huge computing power relied on by the large-scale deep model, and the final result can be obtained, which solves the problem of the complexity of obtaining the data basis and the high computing power requirements of the computing equipment in the molecular dynamics simulation in the calculation process of the force.

[0168] Reference Figure 5 , the electronic device 500 may include one or more of the following components: a processing component 502 , a memory 504 , a power component 506 , a multimedia component 508 , an audio component 510 , an input / output (I / O) interface 512 , a sensor component 514 , and a communication component 516 .

[0169] The processing component 502 generally controls the overall operation of the electronic device 500, such as operations associated with display, phone calls, data communications, camera operations, and recording operations. The processing component 502 may include one or more processors 520 to execute instructions to complete all or part of the steps of the above-mentioned method. In addition, the processing component 502 may include one or more modules to facilitate the interaction between the processing component 502 and other components. For example, the processing component 502 may include a multimedia module to facilitate the interaction between the multimedia component 508 and the processing component 502.

[0170] The memory 504 is used to store various types of data to support the operation of the electronic device 500. Examples of such data include instructions for any application or method operating on the electronic device 500, contact data, phone book data, messages, pictures, multimedia, etc. The memory 504 can be implemented by any type of volatile or non-volatile storage device or a combination thereof, such as static random access memory (SRAM), electrically erasable programmable read-only memory (EEPROM), erasable programmable read-only memory (EPROM), programmable read-only memory (PROM), read-only memory (ROM), magnetic memory, flash memory, magnetic disk or optical disk.

[0171] The power supply component 506 provides power to the various components of the electronic device 500. The power supply component 506 may include a power management system, one or more power supplies, and other components associated with generating, managing, and distributing power to the electronic device 500.

[0172] The multimedia component 508 includes an interface that provides an output interface between the electronic device 500 and the user. In some embodiments, the interface may include a liquid crystal display (LCD) and a touch panel (TP). If the interface includes a touch panel, the interface may be implemented as a touch screen to receive input signals from the user. The touch panel includes one or more touch sensors to sense touch, slide, and gestures on the touch panel. The touch sensor may not only sense the boundaries of the touch or slide action, but also detect the duration and pressure associated with the touch or slide operation. In some embodiments, the multimedia component 508 includes a front camera and / or a rear camera. When the electronic device 500 is in an operating mode, such as a shooting mode or a multimedia mode, the front camera and / or the rear camera may receive external multimedia data. Each front camera and rear camera may be a fixed optical lens system or have a focal length and optical zoom capability.

[0173] The audio component 510 is used to output and / or input audio signals. For example, the audio component 510 includes a microphone (MIC), and when the electronic device 500 is in an operation mode, such as a call mode, a recording mode, and a voice recognition mode, the microphone is used to receive an external audio signal. The received audio signal can be further stored in the memory 504 or sent via the communication component 516. In some embodiments, the audio component 510 also includes a speaker for outputting audio signals.

[0174] The input / output I / O interface 512 provides an interface between the processing component 502 and the peripheral interface module, which may be a keyboard, a click wheel, buttons, etc. These buttons may include but are not limited to: a home button, a volume button, a start button, and a lock button.

[0175] The sensor assembly 514 includes one or more sensors for providing various aspects of status assessment for the electronic device 500. For example, the sensor assembly 514 can detect the open / closed state of the electronic device 500, the relative positioning of components, such as the display and keypad of the electronic device 500, and the sensor assembly 514 can also detect the position change of the electronic device 500 or a component of the electronic device 500, the presence or absence of user contact with the electronic device 500, the orientation or acceleration / deceleration of the electronic device 500, and the temperature change of the electronic device 500. The sensor assembly 514 may include a proximity sensor configured to detect the presence of nearby objects without any physical contact. The sensor assembly 514 may also include an optical sensor, such as a CMOS or CCD image sensor, for use in imaging applications. In some embodiments, the sensor assembly 514 may also include an accelerometer, a gyroscope sensor, a magnetic sensor, a pressure sensor, or a temperature sensor.

[0176] The communication component 516 is used to facilitate wired or wireless communication between the electronic device 500 and other devices. The electronic device 500 can access a wireless network based on a communication standard, such as WiFi, a carrier network (such as 2G, 3G, 4G or 5G), or a combination thereof. In an exemplary embodiment, the communication component 516 receives a broadcast signal or broadcast-related information from an external broadcast management system via a broadcast channel. In an exemplary embodiment, the communication component 516 also includes a near field communication (NFC) module to facilitate short-range communication. For example, the NFC module can be implemented based on radio frequency identification (RFID) technology, infrared data association (IrDA) technology, ultra-wideband (UWB) technology, Bluetooth (BT) technology and other technologies.

[0177] In an exemplary embodiment, the electronic device 500 may be implemented by one or more application-specific integrated circuits (ASICs), digital signal processors (DSPs), digital signal processing devices (DSPDs), programmable logic devices (PLDs), field programmable gate arrays (FPGAs), controllers, microcontrollers, microprocessors, or other electronic components to implement the methods provided in the embodiments of the present application.

[0178] In an exemplary embodiment, a non-transitory computer-readable storage medium including instructions is also provided, such as a memory 504 including instructions, and the instructions can be executed by a processor 520 of an electronic device 500 to perform the above method. For example, the non-transitory storage medium can be a ROM, a random access memory (RAM), a CD-ROM, a magnetic tape, a floppy disk, an optical data storage device, etc.

[0179] Figure 6600 is a block diagram of an electronic device 600 according to another embodiment of the present invention. For example, the electronic device 600 may be provided as a server. Figure 6 , the electronic device 600 includes a processing component 622, which further includes one or more processors, and a memory resource represented by a memory 632, for storing instructions that can be executed by the processing component 622, such as an application. The application stored in the memory 632 may include one or more modules, each corresponding to a set of instructions. In addition, the processing component 622 is configured to execute instructions to perform the method provided in the embodiment of the present application.

[0180] The electronic device 600 may also include a power supply component 626 configured to perform power management of the electronic device 600, a wired or wireless network interface 650 configured to connect the electronic device 600 to a network, and an input / output (I / O) interface 658. The electronic device 600 may operate based on an operating system stored in the memory 632, such as Windows Server™, Mac OS X™, Unix™, Linux™, FreeBSD™ or the like.

[0181] Those skilled in the art will readily appreciate other embodiments of the present application after considering the specification and practicing the application disclosed herein. The present application is intended to cover any modification, use or adaptation of the present application, which follows the general principles of the present application and includes common knowledge or customary techniques in the art that are not disclosed in the present disclosure. The specification and examples are intended to be exemplary only, and the true scope and spirit of the present application are indicated by the following claims.

[0182] It should be understood that the present application is not limited to the precise structures that have been described above and shown in the drawings, and that various modifications and changes may be made without departing from the scope thereof. The scope of the present application is limited only by the appended claims.

Claims

1. A method for determining the force of a perturbed molecular conformation, characterized in that: include: Obtaining conformational sequences of molecules and mechanical perturbation data of the molecules; The conformational sequence comprises a plurality of initial conformations of the molecule; The multiple initial conformations correspond one-to-one to the moments in the preset time series; each initial conformation is used to characterize the spatial position of each atom in the molecule at the corresponding moment; each initial conformation has a corresponding initial force value; Determining a first initial conformation and a second initial conformation in the conformation sequence according to a selection of a target moment in the time sequence; The first initial conformation corresponds to the target moment, and the second initial conformation corresponds to a moment before the target moment; Applying the mechanical perturbation data to the first initial conformation of the molecule to obtain a perturbed conformation of the molecule at the target time; Using the first initial conformation and the second initial conformation as sampling data of a local Gaussian distribution, determining the variance of the local Gaussian distribution, and determining the steady-state conformation of the molecule at the target time; Determining, based on the variance, the perturbed conformation, and the steady-state conformation, the conservative force exerted on the perturbed conformation of the molecule at the target time; Determining the conservative force exerted on the perturbed conformation of the molecule at the target time according to the variance, the perturbed conformation, and the steady-state conformation comprises: Determining an average force value of the molecule according to a first initial force value corresponding to the first initial conformation and a second initial force value corresponding to the second initial conformation; Determining a first conformational difference of the molecule according to a difference between the first initial conformation and the steady-state conformation, and determining a second conformational difference of the molecule according to a difference between the steady-state conformation and the second initial conformation; Determining the ratio of the average of the first conformational difference and the second conformational difference to the variance as the third conformational difference of the molecule; The sum of the average force and the third conformational difference is determined as the conservative force on the perturbed conformation of the molecule.

2. The method for determining the force of disturbing molecular conformation according to claim 1, characterized in that: The mechanical perturbation data records the perturbation value corresponding to each atom in the molecule, the first initial conformation includes the spatial coordinates corresponding to each atom in the molecule, and the step of applying the mechanical perturbation data to the first initial conformation of the molecule to obtain the perturbation conformation of the molecule at the target time comprises: The sum of the disturbance value corresponding to the atom in the disturbance value and the spatial coordinate is used as the spatial coordinate of the atom of the molecule at the target time.

3. The method for determining the force of disturbing molecular conformation according to claim 1, characterized in that: The step of using the first initial conformation and the second initial conformation as sampling data of a local Gaussian distribution and determining the variance of the local Gaussian distribution includes: Determining a force matrix of the molecule at the target time according to a first initial force value corresponding to the first initial conformation and a second initial force value corresponding to the second initial conformation; Determining an energy matrix of the molecule at the target time according to the first initial conformation, the second initial conformation and the force matrix; The ratio of the sum of all non-negative components of the energy matrix to the sum of squares of corresponding components in the force matrix is ​​used as the variance of the local Gaussian distribution.

4. The method for determining the force of disturbing molecular conformation according to claim 3, characterized in that: Determining the energy matrix of the molecule at the target time according to the first initial conformation, the second initial conformation and the force matrix includes: Determining a conformational variable matrix of the molecule according to the first initial conformation and the second initial conformation; The conformational variable matrix and the force matrix are multiplied bit by bit to obtain the energy matrix.

5. The method for determining the force of disturbing molecular conformation according to claim 1, characterized in that: Determining the steady-state conformation of the molecule at the target time comprises: Determining an average conformation of the molecule according to the first initial conformation and the second initial conformation; Determining an average force value of the molecule according to a first initial force value corresponding to the first initial conformation and a second initial force value corresponding to the second initial conformation; The product of the force average value and the variance and the sum of the conformation average value are determined as the steady-state conformation.

6. The method for determining the force of disturbing molecular conformation according to claim 1, characterized in that: There are multiple molecules, and the method further comprises: According to the conformational sequences corresponding to the plurality of molecules, the perturbed conformation of each molecule and the conservative force to which each perturbed conformation is subjected are determined respectively; A perturbed conformation data set of the molecule is generated according to the determined plurality of perturbed conformations and the conservation forces corresponding to the perturbed conformations.

7. A device for determining the force of a perturbed molecular conformation, characterized in that include: A sequence acquisition module, used to acquire the conformational sequence of the molecule and the mechanical perturbation data of the molecule; The conformational sequence comprises a plurality of initial conformations of the molecule; The multiple initial conformations correspond one-to-one to the moments in the preset time series; each initial conformation is used to characterize the spatial position of each atom in the molecule at the corresponding moment; each initial conformation has a corresponding initial force value; A sequence extraction module, for determining a first initial conformation and a second initial conformation in the conformation sequence according to the selection of a target moment in the time sequence; the first initial conformation corresponds to the target moment, and the second initial conformation corresponds to a moment before the target moment; A perturbation generating module, used for applying the mechanical perturbation data to the first initial conformation of the molecule to obtain a perturbed conformation of the molecule at the target time; a distribution construction module, used for taking the first initial conformation and the second initial conformation as sampling data of a local Gaussian distribution, determining the variance of the local Gaussian distribution, and determining the steady-state conformation of the molecule at the target time; A force calculation module, used to determine the conservative force exerted on the perturbed conformation of the molecule at the target time according to the variance, the perturbed conformation, and the steady-state conformation; The force calculation module comprises: A force average value submodule, used to determine the force average value of the molecule according to a first initial force value corresponding to the first initial conformation and a second initial force value corresponding to the second initial conformation; a conformational difference pre-calculation submodule, for determining a first conformational difference of the molecule according to a difference between the first initial conformation and the steady-state conformation, and determining a second conformational difference of the molecule according to a difference between the steady-state conformation and the second initial conformation; a conformational difference calculation submodule, used for determining a ratio of an average value of the first conformational difference and the second conformational difference to the variance as a third conformational difference of the molecule; The perturbed conformation force submodule is used to determine the sum of the force average value and the third conformation difference as the conservative force exerted on the perturbed conformation of the molecule.

8. An electronic device, characterized in that: include: A processor, a memory for storing instructions executable by the processor; The processor is configured to execute the instructions to implement the method according to any one of claims 1 to 6.

9. A computer-readable storage medium, characterized in that: When the instructions in the computer-readable storage medium are executed by a processor of an electronic device, the electronic device is enabled to perform the method as claimed in any one of claims 1 to 6.

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