JP5970809B2 - Stable bond structure search method, program, and information processing apparatus - Google Patents

Description

  The present invention relates to a stable bond structure search method, a program, and an information processing apparatus.

A method for searching for a stable binding structure between a protein and a compound molecule in water is known.
In the classical molecular dynamics method (MD method: Molecular Dynamics Method), an interaction between particles is set or assumed as a predetermined potential function. For example, assuming that the coupling between particles is a spring connection, a potential function for expressing the coupling force is defined.

JP 2011-221868 A

  As a method for searching for a stable bond structure, a method is considered in which many reference structures are prepared, a structure search is performed independently, and a low potential (position) energy is searched. In this method, since all the reference structures are searched, there is a problem that processing takes time.

  In one aspect, the present invention aims to shorten the search time for a stable bond structure.

In order to achieve the above object, the disclosed stable bond structure searching method is provided. In this stable bond structure search method, the computer has the first momentum distribution of the reference structure including the first substance and the second substance changed by the first interaction between the first substance and the second substance. a first potential energy of one structure, the first material and a second structure initial momentum distribution has changed the reference structure by a second interacting greater than the first interaction with the second material first 2 is calculated, the calculated first potential energy and the second potential energy are compared, and the structure having the smaller compared value is changed in the initial momentum distribution by the second interaction. The process of determining the reference structure for calculating the potential energy of the structure is executed.

  In one embodiment, the search time for a stable bond structure can be shortened.

It is a figure which shows the hardware constitutions of the information processing apparatus of embodiment. It is a block diagram which shows the function of the information processing apparatus of embodiment. It is a figure explaining a search process. It is a figure which shows an example of the process which information processing apparatus performs. It is a flowchart which shows the process of information processing apparatus. It is a figure which shows a comparative example. It is a figure which shows the processing result of the information processing apparatus of embodiment.

Hereinafter, an information processing apparatus according to an embodiment will be described in detail with reference to the drawings.
<Embodiment>
FIG. 1 is a diagram illustrating a hardware configuration of the information processing apparatus according to the embodiment.

  The information processing apparatus 10 is entirely controlled by a CPU (Central Processing Unit) 101. A RAM (Random Access Memory) 102 and a plurality of peripheral devices are connected to the CPU 101 via a bus 108.

  The RAM 102 is used as a main storage device of the information processing apparatus 10. The RAM 102 temporarily stores at least part of an OS (Operating System) program and application programs to be executed by the CPU 101. The RAM 102 stores various data used for processing by the CPU 101.

  A hard disk drive 103, graphic processing device 104, input interface 105, drive device 106, and communication interface 107 are connected to the bus 108.

  The hard disk drive 103 magnetically writes data to and reads data from a built-in disk. The hard disk drive 103 is used as a secondary storage device of the information processing apparatus 10. The hard disk drive 103 stores an OS program, application programs, and various data. As the secondary storage device, a semiconductor storage device such as a flash memory can be used.

  A monitor 104 a is connected to the graphic processing device 104. The graphic processing device 104 displays an image on the screen of the monitor 104a in accordance with a command from the CPU 101. Examples of the monitor 104a include a display device using a CRT (Cathode Ray Tube) and a liquid crystal display device.

  A keyboard 105 a and a mouse 105 b are connected to the input interface 105. The input interface 105 transmits signals sent from the keyboard 105a and the mouse 105b to the CPU 101. Note that the mouse 105b is an example of a pointing device, and other pointing devices can also be used. Examples of other pointing devices include a touch panel, a tablet, a touch pad, and a trackball.

  The drive device 106 reads data recorded on a portable recording medium such as an optical disc on which data is recorded so as to be readable by reflection of light or a USB (Universal Serial Bus) memory. For example, when the drive device 106 is an optical drive device, data recorded on the optical disc 200 is read using a laser beam or the like. Examples of the optical disc 200 include Blu-ray (registered trademark), DVD (Digital Versatile Disc), DVD-RAM, CD-ROM (Compact Disc Read Only Memory), CD-R (Recordable) / RW (ReWritable), and the like. .

  The communication interface 107 is connected to the network 50. The communication interface 107 transmits / receives data to / from other computers or communication devices via the network 50.

  With the hardware configuration as described above, the processing functions of the present embodiment can be realized. The following functions are provided in the information processing apparatus 10 having a hardware configuration as shown in FIG.

FIG. 2 is a block diagram illustrating functions of the information processing apparatus according to the embodiment.
The information processing apparatus 10 searches for a static and dynamic stable bond structure of protein and compound molecules in water using a molecular dynamics method.

The information processing apparatus 10 includes a parameter reception unit 11, a calculation unit 12, a structure generation unit 13, a comparison unit 14, a convergence determination unit 15, and a structure storage unit 16.
The parameter accepting unit 11 accepts input of three-dimensional coordinates (x, y, z) and momentum (px, py, pz) of each constituent atom of each substance and solvent to be searched for a stable bond structure.

FIG. 3 is a diagram for explaining the search process.
In the present embodiment, a stable binding state in the case where the protein 21 and the compound molecule 22 are combined in a system in which the protein 21 and the compound molecule 22 interact in a solvent 23 such as water is obtained. The protein 21 and the compound molecule 22 are examples of the first substance and the second substance, respectively.

Returning again to FIG.
The calculation unit 12 multiplies the interaction energy between the protein 21 of interest, the compound molecule 22 and the solvent 23 by λ (0 ≦ λ ≦ 1). The calculation unit 12 calculates the potential energy by gradually increasing the interaction energy from λ = 0 (in this embodiment, in increments of 0.1).

FIG. 4 is a diagram illustrating an example of processing executed by the information processing apparatus.
The structure generating unit 13 generates the protein 21 and the reference structure x ₀ of the compound molecule 22 using the parameters received by the parameter receiving unit 11 at time t0. The reference structure x ₀ changes with the interaction energy over time.

The structure x ₁ indicates a structure having an interaction energy λ = 0.1 times that of the reference structure x ₀ between time t ₀ and time t 1 after a predetermined time (hereinafter referred to as unit time) has elapsed from time t _0. ing. The structure x ₂ shows a structure having an interaction energy λ = 0.2 times that of the reference structure x ₀ between times t0 and t1.

The calculation unit 12 calculates the potential energy of the structure x ₁ and the structure x ₂ at time t1.
Here, the calculation unit 12 uses the interaction energy λ = 0.2 times when calculating the potential energy. Hereinafter, in calculating the potential energy, the potential energy of the structure x ₁ using the interaction energy λ = 0.2 times is U (x ₁ , 0.2). In calculating the potential energy, the potential energy of the structure x ₂ using the interaction energy λ = 0.2 times is U (x ₂ , 0.2).

Comparing section 14, the potential energy U (x _1, 0.2) of the structure x ₁ and potential energy U (x _2, 0.2) of the structural x ₂ Compare. In the example shown in FIG. 5, it is assumed that the potential energy U (x ₁ , 0.2) of the structure x ₁ is lower than the potential energy U (x ₂ , 0.2) of the structure x ₂ . In this case, the comparison unit 14 employs the structure x ₁ having the lower potential energy as the reference structure having the interaction energy λ = 0.2 times between the times t1 and t2.

  The convergence determination unit 15 determines whether or not the potential energy calculated by the calculation unit 12 is equal to or less than a predetermined threshold value. If the potential energy is equal to or less than the threshold value provided in advance, it is determined that the potential energy has converged, and the structure x corresponding to the potential energy determined to have converged is stored in the structure storage unit 16. Hereinafter, when the structure is not distinguished, it is referred to as a structure x.

On the other hand, when the potential energy is larger than the threshold value provided in advance, the comparison unit 14 determines that the structure energy x ₁ with the lower potential energy is the interaction energy λ = 0.2 times and 0.3 times between the times t1 and t2. Adopt to the reference structure and continue searching. Specifically, the calculating unit 12, at the point of time t2 has elapsed unit of time from the time t1, the adjacent interaction energy lambda = 0.2 times the structures x ₁₁ and the interaction energy lambda = 0.3 times the structure x ₃ calculates the respective potential energy.

Here, the calculation unit 12 uses the interaction energy λ = 0.3 times when calculating the potential energy. Hereinafter, in calculating the potential energy, the potential energy of the structure x ₁₁ using the interaction energy λ = 0.3 times is U (x ₁₁ , 0.3). In the calculation of the potential energy, the potential energy of the structure x ₃ using the interaction energy λ = 0.3 times is U (x ₃ , 0.3).

Comparing section 14, the potential energy U (x _11, 0.3) of the structural x ₁₁ structure x ₃ of the potential energy U (x _3, 0.3) are compared. If the potential energy U (x ₁₁ , 0.3) is lower, the structure generating unit 13 converts the structure x ₁₁ having the lower potential energy into an interaction energy λ = 0.3 times between times t2 and t3. And 0.4 times the standard structure.

  In this way, the structures generated with different interaction energies λ are compared, and the structure with the lower potential energy is adopted and the search is continued to generate the interaction energy λ = 0.1 times. A search at another interaction energy λ of structure x (λ = 0.2, 0.3 times in FIG. 4) becomes possible. Therefore, the possibility of reaching a stable bond structure can be increased.

Next, processing of the information processing apparatus will be described using a flowchart.
FIG. 5 is a flowchart showing processing of the information processing apparatus.
[Step S <b> 1] The parameter receiving unit 11 receives input of coordinates and momentum of each constituent atom of the protein 21, the compound molecule 22, and the solvent 23. Thereafter, the process proceeds to step S2.

[Step S2] The calculation unit 12 sets the interaction energy λ = 0. Thereafter, the process proceeds to step S3.
[Step S3] calculating section 12 calculates the potential energy of the reference structure x ₀ generated by input accepted at step S1. Specifically, λHa + (1−λ) Hb is calculated. Ha and Hb are Hamiltonians. Thereafter, the process proceeds to step S4.

[Step S4] The calculation unit 12 adds 0.1 to the interaction energy λ. Then, the process proceeds to step S5.
[Step S5] The calculation unit 12 determines whether or not the interaction energy λ = 1. If the interaction energy λ = 1 (Yes in step S5), the process proceeds to step S6. If not λ = 1 (No in step S5), the process proceeds to step S3.

  [Step S6] The structure generation unit 13 generates a reference structure using molecular dynamics. After the unit time has elapsed, the process proceeds to step S7. In addition, when it changes from step S10 mentioned later, the structure generation part 13 uses the structure x changed in step S9 for a reference | standard structure.

  [Step S7] The calculation unit 12 calculates the potential energy U (λ (i)) that is the interaction energy λ = (i + 1) times in the structure x of λ = i. In addition, the calculation unit 12 calculates the potential energy U (λ (i + 1)) which is the interaction energy λ = (i + 1) times with the structure x which is the interaction energy λ = (i + 1) times. Here, i has an initial value of 0 and changes in increments of 0.1, and the maximum value is 1. For example, if the interaction energy λi = 0.1 times, the interaction energy λ (i + 1) = 0.2 times. Thereafter, the process proceeds to operation S8.

  [Step S8] The comparison unit 14 determines whether or not the potential energy U (λ (i + 1)) is larger than the potential energy U (λ (i)). When the potential energy U (λ (i + 1)) is larger than the potential energy U (λ (i)) (Yes in step S8), the process proceeds to step S9. When the potential energy U (λ (i + 1)) is equal to or lower than the potential energy U (λ (i)) (No in step S8), the process proceeds to step S10.

  [Step S9] The comparison unit 14 replaces the structure x generated with the interaction energy λ = (i + 1) times with the structure x generated with the interaction energy λ = i. Then, the process proceeds to step S10.

  [Step S10] The convergence determination unit 15 determines whether the larger potential energy compared in step S8 is lower than a threshold value prepared in advance. If the potential energy is lower than the threshold value prepared in advance (Yes in step S10), the process proceeds to step S11. If the potential energy is greater than or equal to the threshold value prepared in advance (No in step S10), the process proceeds to step S6.

[Step S11] The convergence determination unit 15 stores the structure x at the time of convergence in the structure storage unit 16. Thereafter, the process of FIG.
In the process illustrated in FIG. 5, the convergence determination unit 15 determines the convergence of the potential energy using a threshold value prepared in advance. However, the present invention is not limited to this, and all potential energies are calculated up to λ = 1 while repeating the processes in steps S6 to S9, and the structure x having the smallest potential energy is stored in the structure storage unit 16 when the calculation is completed. It may be.

  Further, in the process shown in FIG. 5, the potential energies of the structures x adjacent to each other with the magnification of the interaction energy λ are compared. However, the present invention is not limited to this, and the potential energies of the structures x having the magnification of the interaction energy λ separated by 0.1 times or more may be compared.

FIG. 6 is a diagram illustrating a comparative example.
In the comparative example shown in FIG. 6, 100 reference structures x ₀ having different initial positions in the three-dimensional space of the protein 21 and the compound molecule 22 are prepared, and the interaction energy λ is changed from 0 to 1. Show. Even in this method, as a result, a structure having a low potential energy U can be searched. However, for example, the calculation amount is 10 ⁴ days per one reference structure x ₀ using 160 CPUs.

FIG. 7 is a diagram illustrating a processing result of the information processing apparatus according to the embodiment.
The processing result shown in FIG. 7 shows a case where one reference structure x ₀ having different initial positions in the three-dimensional space of the protein 21 and the compound molecule 22 is prepared, and the interaction energy λ is changed from 0 to 1 times. Show. In the process of changing the interaction energy λ from 0 to 1 times, by allowing the change to the structure x generated by a different interaction energy λ times depending on the magnitude of the potential energy, the original interaction energy λ times It is possible to move to a structure space that has not been searched. As a result, it is possible to reduce the number of reference structure x ₀ in comparison with the comparative example is prepared. Therefore, the amount of calculation can be reduced and the processing time can be shortened.

  As described above, according to the information processing apparatus 10, a structure that has not been searched with the original value of λ is allowed by allowing the change to the structure x generated with potential energy having a different interaction energy λ value. Enabled to move and search. Thereby, it is possible to move to and search the structure space that is not searched with the value of λ at the start of processing. This increases the possibility of reaching the most stable bond structure with a small number of reference structures. Therefore, the processing time can be shortened.

  In the present embodiment, a stable binding structure between a protein and a compound molecule is searched. However, a substance capable of searching for a stable binding structure is not limited to a combination of a protein and a compound molecule. In the present embodiment, the stable binding structure between the protein and the compound molecule is searched. However, the number of substances that search for the stable binding structure is not limited to two, and may be three or more.

  The stable coupling structure search method, program, and information processing apparatus of the present invention have been described based on the illustrated embodiment. However, the present invention is not limited to this, and the configuration of each part has the same function. Can be replaced with any structure having Moreover, other arbitrary structures and processes may be added to the present invention.

Further, the present invention may be a combination of any two or more configurations (features) of the above-described embodiments.
The above processing functions can be realized by a computer. In that case, a program describing the processing contents of the functions of the information processing apparatus 10 is provided. By executing the program on a computer, the above processing functions are realized on the computer. The program describing the processing contents can be recorded on a computer-readable recording medium. Examples of the computer-readable recording medium include a magnetic storage device, an optical disk, a magneto-optical recording medium, and a semiconductor memory. Examples of the magnetic storage device include a hard disk drive, a flexible disk (FD), and a magnetic tape. Examples of the optical disk include a DVD, a DVD-RAM, and a CD-ROM / RW. Examples of the magneto-optical recording medium include an MO (Magneto-Optical disk).

  When distributing the program, for example, a portable recording medium such as a DVD or a CD-ROM in which the program is recorded is sold. It is also possible to store the program in a storage device of a server computer and transfer the program from the server computer to another computer via a network.

  The computer that executes the program stores, for example, the program recorded on the portable recording medium or the program transferred from the server computer in its own storage device. Then, the computer reads the program from its own storage device and executes processing according to the program. The computer can also read the program directly from the portable recording medium and execute processing according to the program. In addition, each time a program is transferred from a server computer connected via a network, the computer can sequentially execute processing according to the received program.

  Further, at least a part of the above processing functions can be realized by an electronic circuit such as a DSP (Digital Signal Processor), an ASIC (Application Specific Integrated Circuit), or a PLD (Programmable Logic Device).

DESCRIPTION OF SYMBOLS 10 Information processing apparatus 11 Parameter reception part 12 Calculation part 13 Structure generation part 14 Comparison part 15 Convergence judgment part 16 Structure storage part 21 Protein 22 Compound molecule 23 Solvent

Claims (6)

In a stable bond structure search method for searching for stable bond structures of at least two substances,
Computer
The first potential energy of the first structure in which the initial momentum distribution of the reference structure including the first substance and the second substance is changed by the first interaction between the first substance and the second substance. When, and a second position energy of the second structure initial momentum distribution of the reference structure by a second interacting greater than the first interaction between the first material and the second material is changed Calculate
Comparing the calculated value of the first potential energy and the second potential energy;
The structure having the smaller compared value is determined as a reference structure for calculating the potential energy of the structure in which the initial momentum distribution is changed by the second interaction.
A method for searching for a stable bond structure , characterized by executing a process. The first potential energy is calculated using the first structure and the second interaction, and the second potential energy is calculated using the second structure and the second interaction. stable bond structure search method characterized, according to claim 1, wherein that. To determined the reference structure, wherein the third potential energy of the third structure initial momentum distribution has changed in the reference structure by a second interaction, third mutual greater than said second interacting Calculating the fourth potential energy of the fourth structure in which the initial momentum distribution of the reference structure is changed by the action;
The method for searching for a stable bond structure according to claim 1, wherein the calculated third potential energy and the fourth potential energy are compared.
Change the magnitude of the interaction energy step by step,
Wherein the first interaction between the second interaction is characterized by a neighboring size when graduated, stable coupling structure search method of claim 1. In a program for searching for stable bond structures of at least two substances,
On the computer,
The first potential energy of the first structure in which the initial momentum distribution of the reference structure including the first substance and the second substance is changed by the first interaction between the first substance and the second substance. When, and a second position energy of the second structure initial momentum distribution of the reference structure by a second interacting greater than the first interaction between the first material and the second material is changed Calculate
Comparing the calculated value of the first potential energy and the second potential energy;
The structure having the smaller compared value is determined as a reference structure for calculating the potential energy of the structure in which the initial momentum distribution is changed by the second interaction.
Characterized in that to execute the processing program. In an information processing device that searches for a stable bond structure of at least two substances,
The first potential energy of the first structure in which the initial momentum distribution of the reference structure including the first substance and the second substance is changed by the first interaction between the first substance and the second substance. When, and a second position energy of the second structure initial momentum distribution of the reference structure by a second interacting greater than the first interaction between the first material and the second material is changed A calculation unit for calculating
The calculated first potential energy and the second potential energy value are compared, and the potential energy of the structure whose initial momentum distribution is changed by the second interaction is compared with the structure having the smaller compared value. A determination unit that determines a reference structure for calculation; and
And having an information processing apparatus.

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