Selection support device, selection support method and program

Abstract

To support efficient selection of a stationary phase in a stationary phase extraction method.SOLUTION: A selection support device 10 supports selection of a stationary phase in a stationary phase extraction method. A structure energy calculation part 113 executes processing of calculating structure energy of a composite body of an adsorption object molecule and one stationary phase molecule out of a plurality of stationary phase molecules using quantum chemical calculation, on each of the plurality of stationary phase molecules. A binding energy calculation part 115 executes processing of calculating binding energy of the adsorption object molecule and the stationary phase molecule on the basis of the structure energy of the composite body, on each of the plurality of stationary phase molecules. An output part 119 outputs output information indicating at least one stationary phase molecule selected on the basis of the binding energy calculated by the binding energy calculation part 115, out of the plurality of stationary phase molecules.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a selection support device, a selection support method, and a program. [Background technology]

[0002] There are known techniques for separating specific substances contained in various samples such as solutions, suspensions, etc. For example, Patent Document 1 discloses a method for selecting an extractant that can efficiently select an optimal extractant for extracting a target extractable substance in a solvent extraction method.

[0003] Solid phase extraction (SPE) is known as one of the methods for separating specific substances contained in various samples such as solutions and suspensions. Solid phase extraction is used to separate or concentrate substances as a pretreatment for chemical analysis. In solid phase extraction, the target substances are extracted by utilizing the presence or absence of adsorption according to the affinity between each substance while the solute contained in the solution or suspension, called the mobile phase, flows through a solid, called the stationary phase.

[0004] Solid-phase extraction methods are classified into a pass-through type, in which impurities are adsorbed to a solid phase (stationary phase), and a retention type, in which the target substance is adsorbed to a solid phase. In the pass-through type, the impurities are adsorbed to the solid phase, and the effluent containing the target substance is used for subsequent analysis. Conversely, in the retention type, the target substance is adsorbed to the solid phase, and then a separate mobile phase is run to elute the target substance, which is then used for subsequent analysis. Therefore, if the affinity between substances can be predicted, it will be possible to promote the adsorption of the target substance or impurities to the solid phase. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 6863132 Summary of the Invention [Problem to be solved by the invention]

[0006] In solid-phase extraction, in order to efficiently extract a target substance, it is necessary to select an appropriate stationary phase for the target substance. However, there are many types of stationary phases, and many combinations of target substances and stationary phases exist. Therefore, it takes time and cost to experimentally confirm all candidate combinations in order to obtain an appropriate combination of target substance and stationary phase.

[0007] The present invention has been made in consideration of the above-mentioned problems, and aims to provide a selection support device etc. capable of supporting efficient selection of a stationary phase in a solid-phase extraction method. [Means for solving the problem]

[0008] (1) In order to achieve the above object, a selection support device according to a first aspect of the present invention comprises: A selection support device for supporting selection of a stationary phase in a solid phase extraction method, comprising: a structural energy calculation unit that executes a structural energy calculation process for calculating a structural energy of a complex between an adsorption target molecule and one of a plurality of stationary phase molecules by using a quantum chemical calculation for each of the plurality of stationary phase molecules; a bond energy calculation unit that executes a bond energy calculation process for calculating a bond energy between the adsorption target molecule and the one stationary phase molecule based on the structural energy of the complex calculated by the structural energy calculation unit for each of the plurality of stationary phase molecules; and an output unit that outputs output information indicating at least one stationary phase molecule selected from the plurality of stationary phase molecules based on the binding energy calculated by the binding energy calculation unit.

[0009] (2) In the selection assistance device described in (1) above, the structural energy calculation unit calculates a plurality of structural energies for one complex based on a plurality of three-dimensional structural models in which the relative positional relationships between the adsorption target molecule and the one stationary phase molecule are different in the structural energy calculation process; The bond energy calculation unit may calculate a plurality of bond energies for the one complex based on the plurality of structural energies calculated by the structural energy calculation unit in the bond energy calculation process.

[0010] (3) In the selection assistance device described in (2) above, the bond energy calculation unit calculates a representative value of the plurality of bond energies for the one complex in the bond energy calculation process; The output unit may output the output information indicating the at least one stationary phase molecule selected from the plurality of stationary phase molecules based on the representative value calculated by the binding energy calculation unit.

[0011] (4) In the selection support device according to any one of (1) to (3), In the structural energy calculation process, the structural energy calculation unit may calculate the structural energy of the complex by performing a structural optimization calculation on a three-dimensional structural model of the complex that combines a three-dimensional structural model of the adsorption target molecule and a three-dimensional structural model of the one stationary phase molecule.

[0012] (5) In the selection assistance device described in (4), In the structural energy calculation process, the structural energy calculation unit may determine a relative positional relationship between the adsorption target molecule and the one stationary phase molecule in a three-dimensional structural model of the complex based on a molecular mechanics method, and calculate the structural energy of the complex by performing the structural optimization calculation on the three-dimensional structural model of the complex in which the adsorption target molecule and the one stationary phase molecule are arranged in the determined positional relationship.

[0013] (6) In the selection support device according to any one of (1) to (5), In the bond energy calculation process, the bond energy calculation unit may calculate the difference between the structural energy of the complex calculated by the structural energy calculation unit and the sum of the structural energy of the adsorption target molecule and the structural energy of the one stationary phase molecule as the bond energy.

[0014] (7) In the selection support device according to any one of (1) to (6), The structural energy calculation unit may calculate a structural energy of the adsorption target molecule by performing a structural optimization calculation on a three-dimensional structure model of the adsorption target molecule, and may calculate a structural energy of each of the plurality of stationary phase molecules by performing a structural optimization calculation on a three-dimensional structure model of each of the plurality of stationary phase molecules.

[0015] (8) In the selection support device according to any one of (1) to (7), The structural energy calculation section may obtain the structural energy of the adsorption target molecule and the structural energies of each of the plurality of stationary phase molecules from a database.

[0016] (9) In order to achieve the above object, a selection support method according to a second aspect of the present invention comprises: A selection support method for supporting selection of a stationary phase in a solid phase extraction method, comprising: A structural energy calculation process is performed for each of the plurality of stationary phase molecules, the structural energy of a complex between the adsorption target molecule and one of the plurality of stationary phase molecules being calculated using quantum chemical calculations; performing a bond energy calculation process for calculating a bond energy between the adsorption target molecule and the one stationary phase molecule based on a structural energy of the complex, for each of the plurality of stationary phase molecules; At least one stationary phase molecule is selected from the plurality of stationary phase molecules based on the binding energy.

[0017] (10) In order to achieve the above object, a program according to a third aspect of the present invention comprises: Computer, a structural energy calculation unit that executes a structural energy calculation process for calculating a structural energy of a complex between the adsorption target molecule and one of the plurality of stationary phase molecules by using a quantum chemical calculation for each of the plurality of stationary phase molecules; a bond energy calculation unit that executes a bond energy calculation process for calculating a bond energy between the adsorption target molecule and the one stationary phase molecule based on the structural energy of the complex, for each of the plurality of stationary phase molecules; The binding energy calculation unit functions as an output unit that outputs output information indicating at least one stationary phase molecule selected from the plurality of stationary phase molecules based on the binding energy calculated by the binding energy calculation unit. Effect of the Invention

[0018] According to the present invention, it is possible to assist in the efficient selection of a stationary phase in a solid-phase extraction method. [Brief description of the drawings]

[0019] [Figure 1] 1 is a block diagram showing a configuration of a selection support device according to a first embodiment. [Diagram 2] FIG. 2 is a diagram showing an example of an input screen of the selection support device according to the first embodiment. [Diagram 3] FIG. 1(a) is a diagram showing an example of a three-dimensional structure model of an adsorption target molecule according to embodiment 1. FIG. 1(b) to (d) are diagrams showing examples of three-dimensional structure models of stationary phase molecules according to embodiment 1, respectively. [Figure 4] 1(a) to 1(c) are diagrams showing examples of a three-dimensional structure model of the complex according to embodiment 1. FIG. [Diagram 5] FIG. 2 is a diagram showing the relationship between structural energy and bond energy in the first embodiment. [Figure 6] FIG. 2 is a diagram showing an example of calculation of binding energy in the first embodiment. [Figure 7] FIG. 4 is a diagram showing an example of an output screen of the selection support device according to the first embodiment. [Figure 8]4 is a flowchart showing the flow of a selection support process executed by the selection support device according to the first embodiment. [Figure 9] 4 is a flowchart showing the flow of a bond energy calculation process executed by the selection support device according to the first embodiment. [Figure 10] FIG. 11 is a diagram showing a configuration of a selection support system according to a second embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Hereinafter, the embodiments will be described in detail with reference to the drawings, in which the same or corresponding parts are denoted by the same reference numerals.

[0021] (Embodiment 1) 1 shows the configuration of a selection support device 10 according to embodiment 1. The selection support device 10 is a device that supports the selection of an appropriate stationary phase for a target substance in solid phase extraction (SPE).

[0022] More specifically, the selection support device 10 calculates and compares the binding energies between each of a plurality of candidate stationary phase molecules and the adsorption target molecule by quantum chemical calculation, narrows down to at least one stationary phase molecule that is likely to be suitable for adsorption of the adsorption target molecule, and presents the narrowed down selection to the user. This allows the user to efficiently select a stationary phase molecule suitable for extracting a target substance from among the plurality of stationary phase molecules.

[0023] Here, the molecules to be adsorbed are molecules that are to be adsorbed to the solid phase (stationary phase) in the solid-phase extraction method. In the pass-through type solid-phase extraction method, impurities are adsorbed to the stationary phase, so the molecules to be adsorbed correspond to the molecules that make up the impurities. In contrast, in the retention type solid-phase extraction method, the target substance is adsorbed to the stationary phase, so the molecules to be adsorbed correspond to the molecules that make up the target substance. The stationary phase molecules are the molecules that make up the stationary phase. The stationary phase is also called an extractant, adsorbent, separating agent, etc., and is a phase that is filled in a column to adsorb and fix the molecules to be adsorbed that are contained in the mobile phase.

[0024] The selection support device 10 is an information processing device such as a personal computer, a tablet terminal, a cloud server, etc. The selection support device 10 includes a control unit 11, a storage unit 12, an operation unit 13, a display unit 14, and a communication unit 15.

[0025] The control unit 11 includes a CPU (Central Processing Unit), a ROM (Read Only Memory), and a RAM (Random Access Memory). The CPU includes a microprocessor or the like and is a central processing unit that executes various processes and calculations, and can also be called a processor. In the control unit 11, the CPU reads out a control program stored in the ROM and controls the operation of the entire selection support device 10 while using the RAM as a work memory.

[0026] The storage unit 12 includes a non-volatile memory such as a flash memory or a hard disk, and serves as a so-called secondary storage device or auxiliary storage device. The storage unit 12 stores programs and data used by the control unit 11 to perform various processes. The storage unit 12 also stores data generated or acquired by the control unit 11 performing various processes.

[0027] The operation unit 13 includes input devices such as a keyboard, a mouse, buttons, a touch pad, and a touch panel, and receives operation inputs from a user.

[0028] The display unit 14 includes a display device such as a liquid crystal display, an organic EL (Electro Luminescence) display, or the like, and displays various images under the control of the control unit 11.

[0029] The communication unit 15 includes a communication interface for communicating with devices external to the selection support device 10. For example, the communication unit 15 communicates with the external devices in accordance with well-known communication standards such as LAN (Local Area Network) and USB (Universal Serial Bus). For example, the communication unit 15 is connected to a communication network N, which is a wide area communication network such as the Internet, and communicates with the external devices via the communication network N.

[0030] The control unit 11 functionally includes an input receiving unit 111, a structural energy calculation unit 113, a bond energy calculation unit 115, a selection unit 117, and an output unit 119. In the control unit 11, the CPU reads out a program stored in the ROM into the RAM, and executes and controls the program, thereby functioning as each of these units.

[0031] The input receiving unit 111 receives input of adsorption target molecules and stationary phase molecules. The input receiving unit 111 displays, for example, an input screen shown in Fig. 2 on the display unit 14. The user operates the operation unit 13 to input a desired adsorption target molecule and a plurality of stationary phase molecules that are candidates for stationary phase molecules suitable for adsorption of the adsorption target molecule to the input screen displayed on the display unit 14.

[0032] Figure 2 shows an example where "NH2-C6H5 (aniline)" is input as the molecule to be adsorbed, and "C8 (octylsilylated silica gel)", "SI (silanol)", and "CN (cyanopropyl silica gel)" are input as stationary phase molecules. The molecular structures of these molecules are outlined below.

[0033] [ka]

[0034] [ka]

[0035] [ka]

[0036] [ka]

[0037] Note that information on a plurality of molecules that the user can select as the adsorption target molecule and the stationary phase molecule is prepared in advance in the storage unit 12, and the user may select the adsorption target molecule and the plurality of stationary phase molecules from the plurality of molecules prepared in advance. The input receiving unit 111 receives the adsorption target molecule and the plurality of stationary phase molecules input by the user in this manner, and determines the molecular formulae of the adsorption target molecule and the plurality of stationary phase molecules to be calculated.

[0038] Returning to Fig. 1, the structural energy calculation unit 113 calculates the structural energy of the adsorption target molecule and each of the structural energies of the multiple stationary phase molecules using quantum chemical calculation. The quantum chemical calculation is a method for analyzing the structure, properties, etc. of an atom or molecule by applying the Schrodinger equation, etc. to the atom or molecule. As a method similar to the quantum chemical calculation, for example, the first-principles calculation, etc. can be mentioned.

[0039] The molecular energy is the energy possessed by a molecule. More specifically, from the viewpoint of quantum mechanics, it is expressed as the sum of the kinetic energy of the nucleus, the kinetic energy of the electron, the interaction energy between the nucleus and electron, the interaction energy between electrons, and the interaction energy between the nuclei and the nuclei, and can be calculated by quantum chemical calculations. The energy other than the kinetic energy of the nucleus is related to the structure of the molecule (structural energy of the molecule), and is the energy possessed by the molecule within the molecule (between molecules if there are adjacent molecules). Interpreted in terms of classical mechanics and molecular structure, it is expressed as the sum of the energy between two atoms bonded by a covalent bond (Bond term), the energy between three atoms bonded by a covalent bond (Angle term), the energy between four atoms bonded by a covalent bond (Dihedral-Angle term), the electrostatic interaction energy (Coulomb term), and the intermolecular interaction energy (van der Waals term), and is approximated by the sum of elementary functions (potential function) with atomic and molecular-specific coefficients with the position of the nucleus as a variable. The structural energy of a molecule is the energy possessed structurally within or between molecules. Structural energy is a comprehensive expression of the energy present within or between such molecules, and can be calculated, for example, by solving the Schrodinger equation, which represents the quantum state within a molecule, in quantum mechanics, or by using a potential function in classical mechanics. The former is called quantum chemical calculation, and the latter is called molecular mechanics method (molecular mechanics calculation) or molecular dynamics method (molecular dynamics calculation).

[0040] In order to calculate the structural energy, the structural energy calculation unit 113 first creates a three-dimensional structural model of each of the single molecules of the adsorption target molecule and the multiple stationary phase molecules. Here, the three-dimensional structural model of a molecule is a model that represents the three-dimensional arrangement of multiple atoms that constitute the molecule, and is used as a calculation system for calculating the structural energy of the molecule. The structural energy calculation unit 113 creates an initial structural model that represents the initial arrangement of each atom before the structural optimization calculation described later is performed as the three-dimensional structural model of each of the adsorption target molecule and the multiple stationary phase molecules.

[0041] FIG. 3(a) shows a three-dimensional structure model of "aniline (NH2-C6H5)", which is an example of a molecule to be adsorbed. FIG. 3(b)-(d) show three-dimensional structure models of "C8", "SI", and "CN", which are examples of stationary phase molecules, respectively. In these three-dimensional structure models, each of the multiple atoms constituting the molecule is represented by a sphere in a three-dimensional virtual space represented by the XYZ coordinate system, and the bonds between the atoms are represented by lines. Note that the size of each atom, the distance between atoms, and the relative positional relationship between atoms in the three-dimensional structure models shown in FIG. 3(a)-(d) are not necessarily the same as those in reality.

[0042] After creating the three-dimensional structure model, the structural energy calculation unit 113 then performs a structural optimization calculation. First, the structural energy calculation unit 113 calculates the structural energy of the adsorption target molecule by performing a structural optimization calculation on the three-dimensional structure model of the adsorption target molecule. Second, the structural energy calculation unit 113 calculates the structural energy of each of the multiple stationary phase molecules by performing a structural optimization calculation on each of the three-dimensional structure models of the multiple stationary phase molecules.

[0043] Here, structural optimization calculation means finding a chemically stable molecular conformation by molecular structure calculation. The magnitude of the structural energy of a molecule generated within a molecule changes depending on the positional relationship of the multiple atoms that make up the molecule. More specifically, the distance between atoms changes depending on the bond length between two atoms, the bond angle between three atoms, the degree of twisting between four or more atoms, etc., and the structural energy of the molecule also changes accordingly. Structural optimization calculation is equivalent to searching for a positional relationship where the gradient of such structural energy becomes 0 on the energy surface, that is, where it is minimal. A structure in which the atoms are arranged in a positional relationship where the structural energy is minimal is called an optimized structure.

[0044] The structural optimization calculation will be specifically described below. The structural energy calculation unit 113 first calculates the force acting on each atom constituting the molecule in the initial structural model, and moves each atom slightly in the direction of the force. This causes the energy to drop slightly, and the force acting on each atom also becomes slightly smaller. If each atom is further moved in the direction of the force, a force in the opposite direction may act beyond the optimized structure. If the step of moving each atom in such a force direction is repeated, the magnitude of the force gradually decreases, and finally the force acting on all atoms becomes 0. The structure at this time becomes the optimized structure. The structural energy calculation unit 113 derives the energy in such an optimized structure as structural energy.

[0045] The structural energy calculation unit 113 can use, as a method for calculating structural energy by structural optimization calculation, for example, ab initio molecular orbital methods such as the Hartree-Fock method, the Meller-Plesset perturbation method, the configuration interaction method, and the coupled cluster method, semi-empirical molecular orbital methods such as MNDO, AM1, and PM6, or density functional methods. In addition, the structural energy calculation unit 113 can use, as software for calculating structural energy by structural optimization calculation, existing programs such as Gaussian, GAMESS, Molpro, VASP, WIEN2k, and OpenMX, or programs created by the user.

[0046] The structural energy calculation unit 113 executes a process of creating such a three-dimensional structure model and a process of performing a structural optimization calculation on the created three-dimensional structure model for each of the adsorption target molecule and the multiple stationary phase molecules received as input by the input receiving unit 111. In this way, the structural energy calculation unit 113 calculates optimized structural energies for each of the adsorption target molecule and the multiple stationary phase molecules received as input by the input receiving unit 111.

[0047] After calculating the structural energy of each of the single molecules of the adsorption target molecule and the multiple stationary phase molecules, the structural energy calculation unit 113 then calculates the structural energy of a complex between the adsorption target molecule and the stationary phase molecule. Here, the complex is a system in which two or more molecules are complexed, and is a system in which the adsorption target molecule and the stationary phase molecule are combined. The complex is formed when the adsorption target molecule and the stationary phase molecule become close enough to each other to exert an intermolecular interaction, and the stationary phase molecule adsorbs the adsorption target molecule.

[0048] The structural energy calculation unit 113 executes a structural energy calculation process for calculating the structural energy of a complex between one adsorption target molecule and one stationary phase molecule for each of the multiple stationary phase molecules. In this way, the structural energy calculation unit 113 calculates the structural energy of each of the multiple complexes that correspond one-to-one to the multiple stationary phase molecules. Here, each of the multiple complexes is a complex of one stationary phase molecule among the multiple stationary phase molecules received as input by the input receiving unit 111 and an adsorption target molecule received as input by the input receiving unit 111.

[0049] In order to calculate the structural energy of the complex, the structural energy calculation unit 113 first creates a three-dimensional structural model of the complex. Here, the three-dimensional structural model of the complex is a model that represents the three-dimensional arrangement of a plurality of molecules and a plurality of atoms that constitute the complex, and is used as a calculation system for calculating the structural energy of the complex. As the three-dimensional structural model of the complex, the structural energy calculation unit 113 creates an initial structural model that represents the initial arrangement of each atom before a structural optimization calculation described later is performed.

[0050] More specifically, the structural energy calculation unit 113 creates an initial structural model of the complex by combining a three-dimensional structural model of one of the adsorption target molecules and a three-dimensional structural model of one of the stationary phase molecules. At that time, the structural energy calculation unit 113 uses the three-dimensional structural models after the structural optimization calculation is performed by the structural energy calculation unit 113 as the three-dimensional structural model of one of the adsorption target molecules and the three-dimensional structural model of one of the stationary phase molecules.

[0051] Figures 4(a) to (c) show a three-dimensional structural model of the complex of "aniline" and "C8". Here, the molecules to be adsorbed and the stationary phase molecules that compose the complex can be arranged three-dimensionally in various positional relationships. Therefore, Figures 4(a) to (c) show three examples in which the molecules to be adsorbed and the stationary phase molecules are arranged in different relative positional relationships. Note that the arrangements in Figures 4(a) to (c) are merely examples and are not necessarily the same as the actual arrangements.

[0052] The structural energy calculation unit 113 creates a plurality of three-dimensional structure models with different relative positional relationships between the adsorption target molecule and the stationary phase molecule for the complex of "aniline" and "C8" as shown in Figs. 4(a) to (c). Similarly, the structural energy calculation unit 113 creates a plurality of three-dimensional structure models with different relative positional relationships between the adsorption target molecule and the stationary phase molecule for the complex of "aniline" and "SI" and the complex of "aniline" and "CN". Here, the number of the plurality of structures may be any number, but the following description will be given with an example of 10 structures. In this way, the structural energy calculation unit 113 creates a plurality of three-dimensional structure models with different relative positional relationships between the adsorption target molecule and the stationary phase molecule for each of the plurality of stationary phase molecules.

[0053] More specifically, in the structural energy calculation process, the structural energy calculation unit 113 determines the relative positional relationship between one adsorption target molecule and one stationary phase molecule in the three-dimensional structural model of the complex based on the molecular mechanics method. The molecular mechanics method is a method for calculating the stability of molecular conformations and the energy difference between the conformations based on the sum of potential energies due to the forces acting between atoms.

[0054] Specifically, the structural energy calculation unit 113 uses a molecular mechanics method to determine, with a certain degree of accuracy, a plurality of candidates for the positional relationship in which the two molecules constituting the complex are chemically stable. Then, the structural energy calculation unit 113 creates a plurality of three-dimensional structural models for one complex as shown in Figs. 4(a) to (c) by arranging the adsorption target molecule and the stationary phase molecule in each of the determined positional relationships of the plurality of candidates. In this way, by determining the positional relationship between the adsorption target molecule and the stationary phase molecule with a certain degree of accuracy by the molecular mechanics method, it is possible to reduce the time required for structural optimization calculation, which will be described later, compared to arranging the two molecules randomly.

[0055] After creating the three-dimensional structure model of the complex, the structural energy calculation unit 113 then performs a structural optimization calculation. The structural energy calculation unit 113 calculates the structural energy of the complex by performing a structural optimization calculation on the three-dimensional structure model of the complex in which one adsorption target molecule and one stationary phase molecule are arranged in a positional relationship determined based on a molecular mechanics method.

[0056] The structural optimization calculations performed on the complex are the same as those performed on the individual adsorption target molecules and the individual stationary phase molecules. However, in the structural optimization calculations performed on a single molecule, as described above, a positional relationship in which the structural energy generated within one molecule is minimized is searched for. In contrast, in the structural optimization calculations performed on a complex, in addition to the structural electrostatic energy generated within each molecule, the interaction generated between the two molecules that make up the complex is also taken into consideration to search for a positional relationship in which the structural energy of the entire complex is minimized.

[0057] Specifically, the structural energy calculation unit 113 first calculates the force acting on each atom constituting the molecule for each of the two molecules constituting the complex in the initial structural model, and moves each atom slightly in the direction of the force. This step of moving each atom in the direction of the force is repeated, and the structure in which the forces acting on all atoms in the complex are finally zero becomes the optimized structure of the complex. The structural energy calculation unit 113 derives the energy in such an optimized structure as the structural energy of the complex.

[0058] The structural energy calculation unit 113 executes a process of creating such a three-dimensional structure model and a process of performing a structural optimization calculation on the created three-dimensional structure model in a structural energy calculation process that calculates the structural energy of one complex. The structural energy calculation unit 113 executes such a structural energy calculation process for each of a plurality of stationary phase molecules and for each of a plurality of arrangements in which the relative positional relationship between the adsorption target molecule and the stationary phase molecule is different. As a result, the structural energy calculation unit 113 calculates an optimized structural energy for each of a plurality of stationary phase molecules and for each of a plurality of arrangements.

[0059] 1, the bond energy calculation unit 115 calculates the bond energy between the adsorption target molecule and the stationary phase molecule based on the structural energy of the complex calculated by the structural energy calculation unit 113. The bond energy calculation unit 115 executes such a bond energy calculation process for each of the multiple stationary phase molecules.

[0060] Here, the bond energy is also called adsorption energy, binding energy, etc., and is a value indicating the strength of the bond and adsorption between two molecules. The bond energy between the adsorption target molecule and the stationary phase molecule corresponds to the difference in structural energy between when the adsorption target molecule and the stationary phase molecule exist separately and when they form a complex.

[0061] More specifically, as shown in FIG. 5, the structural energy E12 of the complex between the adsorption target molecule and the stationary phase molecule may differ from the sum of the structural energy E1 of the single molecule of the adsorption target molecule and the structural energy E2 of the single molecule of the stationary phase molecule. The difference corresponds to the bond energy ΔE between the adsorption target molecule and the stationary phase molecule. More specifically, the bond energy ΔE is calculated as a negative value using the formula "ΔE=E12-(E1+E2)". Note that the upper end in FIG. 5 corresponds to energy 0, and the structural energies E1, E2, and E12 each have a negative value. When the value of ΔE is negative, the adsorption target molecule is more stable when adsorbed to the stationary phase molecule, but when the value of ΔE is positive, the two molecules are more stable in a single state separated from each other without adsorption.

[0062] The more negative the value of the bond energy ΔE is, the lower the energy after the two molecules are bonded, i.e., the more stable the state after the bond is. Therefore, the more negative the value of the bond energy ΔE is, the stronger the bond between the two molecules and the higher the affinity is; in other words, it means that the adsorption target molecule is more easily adsorbed by the stationary phase molecule. Note that since the bond energy ΔE is expressed as a negative value, a large absolute value of the bond energy ΔE is equivalent to a low bond energy ΔE.

[0063] The bond energy calculation unit 115 calculates a bond energy ΔE which is the difference between the structural energy E12 of a complex between one of the multiple stationary phase molecules and the adsorption target molecule and the sum of the structural energy E2 of the one stationary phase molecule and the structural energy E1 of the adsorption target molecule. The bond energy calculation unit 115 executes such a bond energy calculation process for each of the multiple stationary phase molecules received as input by the input receiving unit 111, and for each of multiple arrangements in which the relative positional relationship between the adsorption target molecule and the stationary phase molecule is different.

[0064] For example, when the input receiving unit 111 receives input of three stationary phase molecules, "C8", "SI", and "CN", and the structural energy calculation unit 113 acquires structural energy of a complex in 10 different arrangements for each stationary phase molecule, the bond energy calculation unit 115 calculates 30 (=3×10) bond energies. As a result, the bond energy calculation unit 115 calculates bond energies in multiple arrangements for each of the complexes made of the three stationary phase molecules, "C8", "SI", and "CN", as shown in FIG. 6. Note that the bond energy values ​​shown in FIG. 6 are merely examples and are not necessarily the same as the actual ones.

[0065] Furthermore, the binding energy calculation unit 115 calculates a representative value of multiple binding energies for each complex, thereby obtaining one binding energy value for each complex.

[0066] As an example, as shown in FIG. 6, the bond energy calculation unit 115 calculates the average value of the bond energy in a plurality of arrangements for each complex as a representative value of the bond energy. If the structural energy of the complex in an arrangement j of the adsorption target molecule and the stationary phase molecule is represented as Ej, the average value ΔE' of the bond energy in 10 arrangements j (j=1 to 10) is calculated by the formula "ΔE'=1 / 10×Σ{Ej-(E1+E2)}". Note that "Σ" represents the sum in 10 arrangements j (j=1 to 10). The bond energy calculation unit 115 calculates the average value ΔE' as a representative value of the bond energy by such a formula.

[0067] In addition, the representative value is not limited to a simple average value as long as it is a value based on the binding energies in a plurality of arrangements. For example, the representative value may be a median value or an average value excluding values ​​that are significantly different from values ​​in other arrangements.

[0068] 1, the selection unit 117 selects at least one stationary phase molecule from among the plurality of stationary phase molecules received as input by the input receiving unit 111, based on the bond energy calculated by the bond energy calculation unit 115. In this way, the selection unit 117 selects candidates for stationary phase molecules suitable for adsorption of the adsorption target molecule from among the plurality of stationary phase molecules.

[0069] More specifically, the selection unit 117 judges whether or not the representative value of the binding energy calculated by the binding energy calculation unit 115 for each of the plurality of stationary phase molecules satisfies a predetermined selection condition. Then, the selection unit 117 selects at least one stationary phase molecule whose representative value of the binding energy satisfies the selection condition as a candidate for a stationary phase molecule suitable for adsorption of the adsorption target molecule.

[0070] Here, the selection conditions are conditions for narrowing down stationary phase molecules suitable for adsorption of the adsorption target molecules from among a plurality of stationary phase molecules. The selection conditions can be set by the user by operating the operation unit 13.

[0071] As an example, the selection condition is satisfied when the representative value of the binding energy is lower than a predetermined threshold value. Alternatively, the selection condition may be satisfied when the representative value of the binding energy is within a predetermined number in descending order. The predetermined number may be, for example, 5, 10, etc.

[0072] The output unit 119 outputs output information indicating at least one stationary phase molecule selected by the selection unit 117. For example, the output unit 119 displays the output information shown in FIG.

[0073] 7 shows an example in which, among "C8", "SI" and "CN", only one stationary phase molecule, "SI", has a representative value of binding energy that satisfies the selection condition. However, this is just an example and is not necessarily the same as the actual one. The output unit 119 may output a plurality of stationary phase molecules selected by the selection unit 117 from a larger number of stationary phase molecules.

[0074] In this way, the output unit 119 presents to the user the estimation result of at least one stationary phase molecule suitable for adsorption of the adsorption target molecule, input of which has been received by the input receiving unit 111. By checking such an output screen, the user can obtain information on the stationary phase molecule suitable for adsorption of the desired adsorption target molecule.

[0075] The selection unit 117 may select one stationary phase molecule having the maximum representative value of the binding energy as the stationary phase molecule suitable for adsorption of the adsorption target molecule. However, the stationary phase molecule having the maximum binding energy is not necessarily the most suitable stationary phase molecule for adsorption of the adsorption target molecule. In particular, in the retention type solid phase extraction method, after the target substance is adsorbed to the stationary phase, it is necessary to extract the target substance by flowing another mobile phase. In this case, if the adsorption (affinity) between the adsorption target molecule and the stationary phase molecule is too strong, it becomes difficult to extract the adsorption target molecule after adsorption.

[0076] Therefore, the selection unit 117 narrows down the stationary phase molecules, among the plurality of stationary phase molecules, to at least one stationary phase molecule that satisfies the selection condition as a candidate stationary phase molecule suitable for adsorption of the adsorption target molecule, in addition to the stationary phase molecule with the maximum binding energy. Then, the output unit 119 presents the at least one stationary phase molecule narrowed down by the selection unit 117 to the user. This allows the user to efficiently select a stationary phase molecule suitable for adsorption of the adsorption target molecule by selecting a stationary phase molecule at his / her own discretion from the presented candidates. In addition, by allowing the user to freely set the selection condition, it becomes possible to flexibly set the condition for narrowing down the stationary phase molecules.

[0077] Next, the flow of the selection support process executed by the selection support device 10 will be described with reference to the flowchart shown in Fig. 8. The selection support process shown in Fig. 8 starts when a user who wishes to obtain information on stationary phase molecules suitable for adsorption of the adsorption target molecules operates the operation unit 13 to input an instruction to start the selection support process to the selection support device 10. The selection support process shown in Fig. 8 is an example of a selection support method.

[0078] When the selection support process is started, the control unit 11 functions as the input receiving unit 111 and receives input of the adsorption target molecule and multiple stationary phase molecules (step S1). The control unit 11 displays, for example, an input screen shown in Fig. 2 on the display unit 14 and receives input of the target adsorption target molecule and multiple candidate stationary phase molecules from the user.

[0079] When the control unit 11 receives the input of the adsorption target molecule and the multiple stationary phase molecules, the control unit 11 functions as a structural energy calculation unit 113 and calculates the structural energy of each of the single molecules of the adsorption target molecule and the multiple stationary phase molecules that have been received (step S2). Specifically, the control unit 11 creates a three-dimensional structural model of each of the adsorption target molecule and the multiple stationary phase molecules that have been received as input, as shown in Figures 3(a) to (d). Then, the control unit 11 performs a structural optimization calculation for each of the created three-dimensional structural models, and calculates the structural energy of the optimized structure.

[0080] After calculating the structural energy, the control unit 11 calculates the binding energy between each of the plurality of stationary phase molecules and the adsorption target molecule (step S3). Details of the binding energy calculation process in step S3 will be described with reference to FIG.

[0081] 9 is started, the control unit 11 selects one of the plurality of stationary phase molecules that have been input (step S31). Then, the control unit 11 sets one arrangement between the input adsorption target molecule and the selected stationary phase molecule (step S32).

[0082] Once the arrangement is set, the control unit 11 functions as a structural energy calculation unit 113 and calculates the structural energy of the complex between the adsorption target molecule whose input has been accepted and the selected stationary phase molecule in the set arrangement (step S33). Specifically, the control unit 11 creates a three-dimensional structural model of the complex in which the adsorption target molecule and the stationary phase molecule are placed in the set arrangement. Then, the control unit 11 performs a structural optimization calculation on the created three-dimensional structural model and calculates the structural energy in the optimized structure.

[0083] When the structural energy of the complex is acquired, the control unit 11 functions as a bond energy calculation unit 115 and calculates the bond energy (step S34). Specifically, the control unit 11 calculates the sum of the structural energy of a single molecule of the adsorption target molecule, among the structural energies calculated in step S2, and the structural energy of a single molecule of the stationary phase molecule selected in step S31. Then, the control unit 11 calculates the difference between the calculated sum and the structural energy of the complex calculated in step S33 as the bond energy of the complex.

[0084] After calculating the bond energy, the control unit 11 judges whether or not the bond energy has been calculated for a predetermined number of different arrangements (step S35). If the bond energy has not been calculated for a predetermined number of different arrangements (step S35; NO), the control unit 11 returns the process to step S32. In this case, the control unit 11 sets another arrangement in which the relative positional relationship between the adsorption target molecules and the stationary phase molecules is different in step S32. Then, the control unit 11 obtains the structural energy of the complex in which the adsorption target molecules and the stationary phase molecules are arranged in the set arrangement, and calculates the bond energy.

[0085] Finally, when the calculation of the binding energies for the predetermined number of different configurations is completed (step S35; YES), the average value of the binding energies calculated for the predetermined number of different configurations is calculated (step S36).

[0086] After calculating the average value of the binding energy, the control unit 11 judges whether or not there are any unselected stationary phase molecules (step S37). If there are any unselected stationary phase molecules (step S37; YES), the control unit 11 returns the process to step S31. In this case, the control unit 11 selects one unselected stationary phase molecule from the multiple stationary phase molecules whose input has been accepted in step S31. Then, the control unit 11 executes the processes of steps S32 to S36 for the complex between the adsorption target molecule whose input has been accepted and the selected stationary phase molecule, and calculates the average value of the binding energies calculated for a predetermined number of different arrangements.

[0087] Finally, when there are no unselected stationary phase molecules (step S37; NO), the control unit 11 ends the binding energy calculation process shown in FIG.

[0088] 8, when the bond energy calculation process is completed, the control unit 11 functions as a selection unit 117 and selects at least one stationary phase molecule from the plurality of stationary phase molecules inputted in step S1 based on the bond energy calculated in step S3 (step S4). Specifically, the control unit 11 selects at least one stationary phase molecule whose average value of the bond energy calculated in step S36 satisfies the selection condition from the plurality of stationary phase molecules inputted.

[0089] When at least one stationary phase molecule is selected, the control unit 11 functions as the output unit 119 and outputs output information indicating the selected at least one stationary phase molecule (step S5). Specifically, the control unit 11 displays, for example, an output screen shown in Fig. 7 on the display unit 14. With the above, the selection support process shown in Fig. 8 is completed.

[0090] As described above, the selection support device 10 according to the first embodiment calculates the structural energy of a complex between the adsorption target molecule and one stationary phase molecule, and executes a process of calculating the bond energy based on the calculated structural energy for each of the multiple stationary phase molecules. Then, the selection support device 10 according to the first embodiment outputs output information indicating at least one stationary phase molecule selected based on the calculated bond energy from among the multiple stationary phase molecules.

[0091] In this way, the selection support device 10 according to the first embodiment calculates the binding energy between each of the multiple candidate stationary phase molecules and the adsorption target molecule using quantum chemical calculations. Therefore, it is not necessary to experimentally confirm whether each of the multiple candidate stationary phase molecules is suitable for adsorption of the adsorption target molecule, and it is easy to try various combinations of stationary phase molecules and adsorption target molecules. As a result, the user can easily narrow down the stationary phase molecules suitable for adsorption of the adsorption target molecule from among the multiple stationary phase molecules, and it becomes possible to efficiently select a stationary phase suitable for extracting the target substance.

[0092] (Embodiment 2) Next, a description will be given of embodiment 2. Descriptions of configurations and functions similar to those of embodiment 1 will be omitted where appropriate.

[0093] In the first embodiment, the structural energy calculation unit 113 creates a three-dimensional structural model for each of the adsorption target molecule and the multiple stationary phase molecules received as input by the input receiving unit 111, and performs structural optimization on the created three-dimensional structural model to obtain the structural energy of each molecule in a single molecule. However, the three-dimensional structural model and structural energy obtained by performing structural optimization calculation of a publicly known molecule may already be known. Therefore, in the second embodiment, the structural energy calculation unit 113 obtains the three-dimensional structural model and structural energy of each of the adsorption target molecule and the multiple stationary phase molecules received as input by the input receiving unit 111 from outside the selection support device 10 through communication.

[0094] 10 shows the overall configuration of the selection support system 1 according to the second embodiment. The selection support system 1 includes a selection support device 10 and a database 20. The database 20 stores data on the structural energy and the three-dimensional structural model after structural optimization for each of a plurality of molecules that may be adsorption target molecules or stationary phase molecules. The database 20 is communicatively connected to the selection support device 10 via a communication network N.

[0095] When the input receiving unit 111 receives the input of the adsorption target molecule and the multiple stationary phase molecules, the structural energy calculation unit 113 communicates with the database 20 via the communication unit 15. As a result, the structural energy calculation unit 113 acquires, from the database 20, a three-dimensional structural model and structural energy after the structural optimization calculation is performed for each of the adsorption target molecule and the multiple stationary phase molecules whose input has been received.

[0096] The structural energy calculation unit 113 creates a three-dimensional structural model of the complex using the respective three-dimensional structural models of the adsorption target molecule and the multiple stationary phase molecules acquired from the database 20. Moreover, the bond energy calculation unit 115 calculates the bond energy using the respective structural energies of the adsorption target molecule and the multiple stationary phase molecules acquired from the database 20. The other processing is the same as in the first embodiment.

[0097] As described above, the selection support device 10 according to the second embodiment acquires the three-dimensional structure model and the structural energy of each of the adsorption target molecule and the plurality of stationary phase molecules through communication from outside the selection support device 10. In this way, by acquiring the three-dimensional structure model and the structural energy of a known molecule from outside, the processing executed in the selection support device 10 can be simplified.

[0098] The structural energy calculation unit 113 is not limited to acquiring all of the three-dimensional structure models and structural energies of the adsorption target molecule and the plurality of stationary phase molecules whose input has been accepted from the database 20. For example, when the three-dimensional structure models and structural energies of some of the adsorption target molecule and the plurality of stationary phase molecules whose input has been accepted are not present in the database 20, the structural energy calculation unit 113 creates and calculates the three-dimensional structure models and structural energies of the some of the molecules in the same manner as in the first embodiment. Then, the structural energy calculation unit 113 may acquire the three-dimensional structure models and structural energies of the remaining molecules from the database 20.

[0099] Further, the database 20 is not limited to being provided outside the selection support device 10, and may be provided inside the selection support device 10.

[0100] (Modification) Although the embodiments have been described above, it is possible to combine the embodiments, or to modify or omit the embodiments as appropriate.

[0101] For example, the molecules to be adsorbed and the stationary phase molecules given in the above embodiment are merely examples, and other molecules may be the molecules to be adsorbed or the stationary phase molecules.

[0102] In the above embodiment, the selection support device 10 includes the operation unit 13 and the display unit 14, which function as a user interface. However, the selection support device 10 may not include the operation unit 13 and the display unit 14. An external device communicatively connected to the selection support device 10 via a communication network N may include a user interface corresponding to the operation unit 13 and the display unit 14. In this case, the input receiving unit 111 receives input of the adsorption target molecule and the multiple stationary phase molecules from the external device via the communication unit 15 and the communication network N. In addition, the output unit 119 outputs output information to the external device via the communication unit 15 and the communication network N.

[0103] In the above embodiment, the output unit 119 displays the output information on the display unit 14 as shown in Fig. 7. However, the output unit 119 is not limited to displaying the output information, and may output the output information to a device external to the selection support device 10, for example, through communication by the communication unit 15. Alternatively, the output unit 119 may output the output information as sound from a speaker.

[0104] In the above embodiment, the selection support device 10 includes the input receiving unit 111, the structural energy calculation unit 113, the bond energy calculation unit 115, the selection unit 117, and the output unit 119. However, all of these units are not limited to being provided in one device. At least one of these units may be provided in a distributed manner in different devices communicatively connected via a communication network N. For example, each unit of the control unit 11 may be provided in a distributed manner in multiple independent devices, and the process described in the above embodiment may be executed while transmitting and receiving necessary data via the communication network N. Even if each unit is provided in a distributed manner in multiple devices, the multiple devices may be collectively referred to as the selection support device 10.

[0105] In the above embodiment, the control unit 11 functions as each of the input receiving unit 111, the structural energy calculation unit 113, the bond energy calculation unit 115, the selection unit 117, and the output unit 119 by the CPU executing the program stored in the ROM or the storage unit 12. However, the control unit 11 may be dedicated hardware. The dedicated hardware is, for example, a single circuit, a composite circuit, a programmed processor, an ASIC (Application Specific Integrated Circuit), an FPGA (Field-Programmable Gate Array), or a combination thereof. When the control unit 11 is dedicated hardware, the functions of each unit may be realized by individual hardware, or the functions of each unit may be realized together by a single piece of hardware.

[0106] In addition, some of the functions of each unit may be realized by dedicated hardware, and other parts may be realized by software or firmware. In this way, the control unit 11 can realize each of the above-mentioned functions by hardware, software, firmware, or a combination of these.

[0107] It is also possible to cause an existing computer, such as a personal computer or a cloud server, to function as the above-mentioned selection support device 10 by applying a program that defines the operation of the above-mentioned selection support device 10 to the existing computer.

[0108] Furthermore, such programs may be distributed in any manner, and may be distributed by storing them on a computer-readable recording medium such as a CD-ROM (Compact Disk ROM), a DVD (Digital Versatile Disk), an MO (Magneto Optical Disk), or a memory card, or may be distributed via a communications network such as the Internet.

[0109] The above describes preferred embodiments of the present invention. However, the present invention is not limited to the above-described embodiments, and various modifications and substitutions can be made to the above-described embodiments without departing from the scope of the claims. [Explanation of symbols]

[0110] 1. Selection Support System 10 Selection aid 11 Control section 12 Storage section 13 Control section 14 Display section 15 Communications Department 20 Database 111 Input reception section 113 Structural Energy Calculation Department 115 Binding Energy Calculation Section 117 Sorting Department 119 Output section N Communication Network

Claims

1. A selection support device for supporting selection of a stationary phase in a solid phase extraction method, comprising: a structural energy calculation unit that executes a structural energy calculation process for calculating a structural energy of a complex between an adsorption target molecule and one of the plurality of stationary phase molecules by using quantum chemical calculations for each of the plurality of stationary phase molecules; a bond energy calculation unit that executes a bond energy calculation process for calculating a bond energy between the adsorption target molecule and the one stationary phase molecule based on the structural energy of the complex calculated by the structural energy calculation unit for each of the plurality of stationary phase molecules; and an output unit that outputs output information indicating at least one stationary phase molecule selected from the plurality of stationary phase molecules based on the binding energy calculated by the binding energy calculation unit. Selection aids.

2. the structural energy calculation unit calculates a plurality of structural energies for one complex based on a plurality of three-dimensional structural models in which the relative positional relationship between the adsorption target molecule and the one stationary phase molecule is different in the structural energy calculation process; The bond energy calculation unit calculates a plurality of bond energies for the one complex based on the plurality of structural energies calculated by the structural energy calculation unit in the bond energy calculation process. The selection support device according to claim 1 .

3. the bond energy calculation unit calculates a representative value of the plurality of bond energies for the one complex in the bond energy calculation process, The output unit outputs the output information indicating the at least one stationary phase molecule selected based on the representative value calculated by the binding energy calculation unit from among the plurality of stationary phase molecules. The selection assistance device according to claim 2 .

4. the structural energy calculation unit calculates the structural energy of the complex by performing a structural optimization calculation on a three-dimensional structural model of the complex, the three-dimensional structural model of the one stationary phase molecule and the three-dimensional structural model of the adsorption target molecule being combined in the structural energy calculation process; The selection support device according to any one of claims 1 to 3.

5. the structural energy calculation unit, in the structural energy calculation process, determines a relative positional relationship between the adsorption target molecule and the one stationary phase molecule in a three-dimensional structural model of the complex based on a molecular mechanics method, and calculates a structural energy of the complex by performing the structural optimization calculation on the three-dimensional structural model of the complex in which the adsorption target molecule and the one stationary phase molecule are arranged in the determined positional relationship; The selection assistance device according to claim 4.

6. the bond energy calculation unit calculates, in the bond energy calculation process, a difference between the structural energy of the complex calculated by the structural energy calculation unit and the sum of the structural energy of the adsorption target molecule and the structural energy of the one stationary phase molecule as the bond energy; The selection support device according to any one of claims 1 to 3.

7. the structural energy calculation unit calculates a structural energy of the adsorption target molecule by performing a structural optimization calculation on a three-dimensional structural model of the adsorption target molecule, and calculates a structural energy of each of the plurality of stationary phase molecules by performing a structural optimization calculation on each of the three-dimensional structural models of the plurality of stationary phase molecules. The selection support device according to any one of claims 1 to 3.

8. The structural energy calculation unit acquires the structural energy of the adsorption target molecule and each of the structural energies of the plurality of stationary phase molecules from a database. The selection support device according to any one of claims 1 to 3.

9. A selection support method for supporting selection of a stationary phase in a solid phase extraction method, comprising: A structural energy calculation process is performed for each of the plurality of stationary phase molecules, the structural energy of a complex between the adsorption target molecule and one of the plurality of stationary phase molecules being calculated using quantum chemical calculations; performing a bond energy calculation process for calculating a bond energy between the adsorption target molecule and the one stationary phase molecule based on a structural energy of the complex, for each of the plurality of stationary phase molecules; selecting at least one stationary phase molecule from the plurality of stationary phase molecules based on the binding energy; Selection aid methods.

10. Computer, a structural energy calculation unit that executes a structural energy calculation process for calculating a structural energy of a complex between an adsorption target molecule and one of the plurality of stationary phase molecules by using a quantum chemical calculation for each of the plurality of stationary phase molecules; a bond energy calculation unit that executes a bond energy calculation process for calculating a bond energy between the adsorption target molecule and the one stationary phase molecule based on the structural energy of the complex, for each of the plurality of stationary phase molecules; an output unit that outputs output information indicating at least one stationary phase molecule selected based on the binding energy calculated by the binding energy calculation unit from among the plurality of stationary phase molecules; program.

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