JP5942571B2 - Calculation support program, calculation support apparatus, and calculation support method - Google Patents

Description

  The present invention relates to a calculation support program, a calculation support apparatus, and a calculation support method.

  Conventionally, as a technique for estimating molecular properties, there is a technique using a molecular orbital method which is a kind of molecular orbital calculation. For example, the molecular orbital interaction energy between a protein and a ligand substance in a water-soluble complex containing a target protein and a ligand substance that specifically binds to a specific receptor in an aqueous solution. There is a technique for estimating from the calculation result of the law.

In addition, there is a dielectric model in which solvent molecule models that simulate solvent molecules are distributed around the target molecule model that simulates the target molecule in the solution model, and is uniformly polarized around the target molecule model. There is a technique for executing the molecular orbital method. This technique, for example, if you want to calculate the value of a, want to reduce the error of the calculation as an acid dissociation constant pK _a which is one of the indicators of the strength of the acid, the experimental result of the calculation results and the target molecule of interest molecule and Can be set to 1 [kcal] unit. (For example, see Patent Document 1 and Non-Patent Document 1 below.)

JP 2010-117986 A

Junming Ho, et al., “A universal approach for continuum solvent pKa calibrations: are the year yet?”, Theoretical Chemistry Accounts, Vol. 125, 2010, p. 3-21

  However, in the above-described conventional technology, when the solvent molecule model is arranged around the target molecule model in the solution model, it is difficult to determine where the solvent arrangement model is arranged. For example, if the molecular orbital method is executed by deciding to place the solvent molecular model at a position where the solvent molecular model is not actually placed, the physical property value resulting from the calculation and the actual physical property value will deviate, The calculation accuracy of physical properties deteriorates.

  An object of the present invention is to provide a calculation support program, a calculation support apparatus, and a calculation support method capable of improving the calculation accuracy of physical property values in order to eliminate the above-described problems caused by the prior art.

  In order to solve the above-described problems and achieve the object, according to one aspect of the present invention, a first point is set for each point of the point group set on the surface covering the first molecular model arranged on the spatial coordinates. The potential value at the point is calculated with reference to the storage unit that stores the charge value of each atomic model in the molecular model of the first model, and the first value is calculated based on the potential value at the calculated point from the point group. A calculation support program, a calculation support apparatus, and a calculation support method for determining an arrangement point at which a second molecular model forming a molecular model and a second molecular model forming a solution model are combined are proposed.

  According to one aspect of the present invention, it is possible to improve the calculation accuracy of physical property values.

FIG. 1 is an explanatory diagram illustrating an operation example of the calculation support apparatus according to the present embodiment. FIG. 2 is a block diagram illustrating a hardware configuration example of the calculation support apparatus. FIG. 3 is an explanatory diagram showing an example of the stored contents of the user setting data. FIG. 4 is an explanatory diagram showing an example of the stored contents of atomic information data. FIG. 5 is an explanatory diagram showing an example of the contents stored in the solvent arrangement plane data. FIG. 6 is an explanatory diagram showing an example of the storage contents of the solvent molecule setting data. FIG. 7 is a block diagram illustrating a functional configuration example of the calculation support apparatus. FIG. 8 is an explanatory view showing an arrangement example of a solvent molecule model. FIG. 9 is an explanatory diagram showing an example of a method of extracting lattice points after the solvent molecule model is arranged. FIG. 10 is an explanatory diagram showing an example of the arrangement of the solvent molecule model in the second layer. FIG. 11 is a flowchart illustrating an example of the arrangement processing procedure. FIG. 12 is a flowchart illustrating an example of an additional point setting process procedure.

  Exemplary embodiments of a disclosed calculation support program, a calculation support apparatus, and a calculation support method will be described below in detail with reference to the accompanying drawings.

  FIG. 1 is an explanatory diagram illustrating an operation example of the calculation support apparatus according to the present embodiment. The calculation support apparatus 101 is an apparatus that supports processing for estimating the physical property value of the first molecule in the solution by molecular orbital calculation. A solution is a mixture consisting of two or more substances and forming a uniform phase. A solution is referred to as a mixed gas if the uniform phase is a gas, a solution if the uniform phase is liquid, and a solid solution if the uniform phase is solid. The molecular orbital calculation includes a molecular orbital method, a density functional method, a valence bond method, and the like.

  As specific support contents, the calculation support apparatus 101 places the second molecule in the solution at a position where the first molecule model imitating the first molecule in the solution model imitating the solution easily interacts. A simulated second molecular model is placed. After arrangement of the second molecule, the calculation support apparatus 101 estimates the physical property value of the first molecule by molecular orbital calculation. Alternatively, the result of arranging the second molecular model may be output, and another apparatus may execute processing for estimating the physical property value of the first molecule by molecular orbital calculation.

  Hereinafter, in the present embodiment, it is assumed that the solution is a liquid. Accordingly, the first molecule becomes a solute and the second molecule becomes a solvent. Hereinafter, the first molecule is referred to as “target molecule”. The second molecule is referred to as “solvent molecule”. Note that the solvent may contain one type of molecule or may contain a plurality of types of molecules. The first molecular model is referred to as a “target molecular model”. A molecular model that serves as a solvent other than the first molecular model is referred to as a “solvent molecular model”. For example, the second molecular model is referred to as a “solvent molecule model”. The third molecular model that becomes another solvent molecule is referred to as “another solvent molecule model”. 1 to 12 are indicated by “atom_ (symbol)” with respect to the atoms indicated by the symbols enclosed in parentheses. For example, when a symbol “(1)” is given to a hydrogen atom “H” on the drawing, it is described as H_ (1).

  The diagram shown in FIG. 1 shows a solution model generated by the calculation support apparatus 101 executing molecular design support software. It is assumed that the solution model approximates the solvent molecule model 121 as a uniformly polarized dielectric model 110, and the target molecule model 111 is in the dielectric model 110. The solution model is developed on the space coordinates, and the target molecule model 111 is arranged on the space coordinates.

  The target molecule model 111 and the solvent molecule model 121 are models used to help the user of the calculation support apparatus 101 understand the target molecule and the solvent molecule by visualizing them. In the model, atoms are represented as spheres, and bonds are represented as bars, and there are several forms depending on the size of the atoms and the thickness of the bonds. As a model format, there are a model in which bonds are represented as a wire, a model in which atoms are represented as spheres, a bond is represented by a bar, a model in which atoms are represented by a sphere reflecting the size of the atomic radius, and the like. In the present embodiment, any model may be used.

  The target molecule model 111 is a model imitating a polymer compound such as a protein, for example. The solvent molecule model 121 may be, for example, a polar molecule model such as water or ethanol, or a nonpolar molecule model such as benzene or toluene. In the solution model, there may be a plurality of types of solvent molecule models.

  The calculation support apparatus 101 calculates the value of the potential at each point in the point group set on the surface 112 covering the target molecule model 111. An electric potential is an electrical potential energy generated by an electric charge in an electrostatic field, and is also called an electrostatic potential. The value of the potential is calculated with reference to the charge value of each atomic model in the target molecule model 111, for example.

  Further, the surface 112 covering the target molecule model 111 only needs to cover the target molecule model 111. For example, the surface 112 may be a surface in which the electron density of the target molecule model 111 has a certain value, or may be a three-dimensional surface in which spheres indicating the van der Waals radii of each atomic model of the target molecule model 111 are combined. Further, the calculation support apparatus 101 may perform processing so that the solvent molecule model 121 is bonded to the surface 112, or may perform processing so that a three-dimensional model including the solvent molecule model 121 is bonded to the surface 112. For example, the calculation support apparatus 101 shown in FIG. 1 determines the position where the cylindrical model 122 is arranged using the cylindrical model 122 including the solvent molecule model 121. In addition to the cylindrical model 122, for example, a model imitating a sphere or a model imitating a cone may be adopted as the three-dimensional model. As to which model is adopted, for example, the model is adopted based on the shape of the solvent molecule model.

  Next, the calculation support apparatus 101 includes a cylinder model including a solvent molecule model 121 that forms a solution model with the target molecule model 111 based on the potential value at the calculated point from the point group set on the surface 112. The arrangement point to which 122 is coupled is determined. In FIG. 1, the difference in potential value in the surface 112 is represented by hatching. The dark hatched portion in the center of the surface 112 indicates that the potential value is positive. The thin hatched portions on the center left and center right in the surface 112 indicate that the potential value is near zero. The hatched portions on the left and right sides in the surface 112 indicate that the potential value is negative. For example, the calculation support apparatus 101 determines, from the point group set on the surface 112, the point (1) with the maximum absolute value of the potential as the arrangement point to which the cylindrical model 122 is coupled.

  As described above, the calculation support apparatus 101 determines the placement point of the solvent molecule model 121 based on the potential of each point on the surface 112 covering the target molecule model 111 when calculating the physical property value of the target molecule in the solution. Thereby, the calculation support apparatus 101 can improve the calculation accuracy of the physical property value because the solvent molecule model 121 is arranged at a position where the interaction is easy to interact. Hereinafter, the calculation support apparatus 101 will be described in detail with reference to FIGS.

  FIG. 2 is a block diagram illustrating a hardware configuration example of the calculation support apparatus. In FIG. 2, the calculation support apparatus 101 includes a CPU (Central Processing Unit) 201, a ROM (Read-Only Memory) 202, and a RAM (Random Access Memory) 203.

  Further, the calculation support apparatus 101 as a storage device includes a magnetic disk drive 204, a magnetic disk 205, an optical disk drive 206, and an optical disk 207. In addition, the calculation support apparatus 101 includes a display 208, an interface (I / F) 209, a keyboard 210, and a mouse 211 as input / output devices for a user and other devices. Each unit is connected by a bus 212.

  Here, the CPU 201 is an arithmetic processing device that controls the entire calculation support apparatus 101. The ROM 202 is a non-volatile memory that stores a program such as a boot program. A RAM 203 is a volatile memory used as a work area for the CPU 201. The magnetic disk drive 204 is a control device that controls reading / writing of data with respect to the magnetic disk 205 according to the control of the CPU 201. The magnetic disk 205 is a non-volatile memory that stores data written under the control of the magnetic disk drive 204.

  The optical disk drive 206 is a control device that controls reading / writing of data with respect to the optical disk 207 according to the control of the CPU 201. The optical disc 207 is a non-volatile memory that stores data written under the control of the optical disc drive 206. Further, the optical disk 207 causes a computer to read data stored on the optical disk 207. Note that the calculation support program according to the present embodiment may be stored in any of the storage devices of the ROM 202, the magnetic disk 205, and the optical disk 207.

  The display 208 is a display device that displays data such as a document, an image, and function information as well as a cursor, an icon, or a tool box. For example, the display 208 can employ a CRT, a TFT liquid crystal display, a plasma display, or the like.

  The I / F 209 is a control device that controls an internal interface with the network 213 and controls input / output of data from an external device. The I / F 209 is connected to a network 213 such as a LAN (Local Area Network), a WAN (Wide Area Network), and the Internet through a communication line, and is connected to another device via the network 213. For example, a modem or a LAN adapter can be adopted as the I / F 209.

  The keyboard 210 has keys for inputting characters, numbers, various instructions, and the like, and is a device for inputting data. The keyboard 210 may be a touch panel type input pad or a numeric keypad. The mouse 211 is a device for moving the cursor, selecting a range, moving the window, changing the size, and the like. The calculation support apparatus 101 may have a trackball, a joystick, or the like as long as it has the same function as a pointing device instead of the mouse 211. Next, user setting data, atomic information data, solvent arrangement plane data, and solvent molecule setting data used in the present embodiment will be described.

  FIG. 3 is an explanatory diagram showing an example of the stored contents of the user setting data. The user setting data 301 stores values set by the user. FIG. 3A shows an example of the contents stored in the user setting data 301. FIG. 3B illustrates the contents indicated by each field of the user setting data 301.

  The user setting data 301 shown in FIG. 3A records a record 301-1. The user setting data 301 includes two fields: the number of solvent molecule model arrangements and the number of solvent molecule model layers. The maximum number of solvent molecule models to be arranged in the target molecule model is stored in the solvent molecule model arrangement number field. The number of layers in which the solvent molecule model is arranged is stored in the number of layers field of the solvent molecule model. For example, the record 301-1 indicates that the number of arranged solvent molecule models is n [pieces] and the number of layers of the solvent molecule model is m [pieces]. Next, the number of layers of the solvent molecule model will be described with reference to FIG.

  FIG. 3B shows a diagram in the case where there are two layers of the solvent molecule model. A layer close to the target molecule model 111 is a first layer, and a layer close to the next molecule is a second layer. The first layer is a space outside the surface 112 covering the target molecule model 111. The second layer includes a target molecule model 111 and solvent molecule models 121-1 to 121-5, and a new target molecule model formed by the cylindrical models 122-1 to 122-5 added to the first layer. It is the space outside the surface to be covered. In FIG. 3B, a cylindrical model 122-6 including a solvent molecule model 121-6 is added to the surface 302 that forms the second layer.

  For example, if the value n = 4 in the arrangement number field of the solvent molecule model, the calculation support apparatus 101 ends the process of arranging the solvent molecule model 121 when the solvent molecule models 121-1 to 121-4 are arranged. . In addition, if the value n of the arrangement number field of the solvent molecule model is 6 and the value m of the number of layers of the solvent molecule model is m = 1, the calculation support apparatus 101 uses the solvent molecule models 121-1 to 121-5. Place. Subsequently, when there is no place where the solvent molecule model 121 is further arranged in the first layer, the calculation support apparatus 101 ends the process of arranging the solvent molecule model 121.

  FIG. 4 is an explanatory diagram showing an example of the stored contents of atomic information data. The atom information data 401 stores information related to the atom model. FIG. 4A shows an example of the stored contents of the atomic information data 401. In FIG. 4B, the contents indicated by each field of the atomic information data 401 are illustrated.

  The atomic information data 401 stores each atomic model in the target molecule model 111 as one record. The atomic information data 401 shown in FIG. 4A stores records 401-1 and 401-2. The atom information data 401 includes three fields: an atom model ID (IDentification), position information, and electric charge. Information for identifying an atomic model is stored in the atomic model ID field. In the position information field, position information of the corresponding atomic model in the spatial coordinate system is stored. The spatial coordinate system may be an orthogonal coordinate system such as an X axis, a Y axis, or a Z axis, or a spherical coordinate system that expresses a position by three elements: a distance from the origin, an angle from one axis, and an angle from another axis. But you can. In this embodiment, an orthogonal coordinate system that is the X axis, the Y axis, and the Z axis is adopted. In the charge field, the charge value of the corresponding atomic model is stored.

For example, the record 401-1 is a carbon atom model whose atomic model ID is C_ (1), the position of the carbon atom model is (x ₁ , y ₁ , z ₁ ), and the charge of the carbon atom model is It shows that it is (delta)-. The record 401-2 is a hydrogen atom model whose atomic model ID is H_ (2), the position of the hydrogen atom model is (x ₂ , y ₂ , z ₂ ), and the charge of the hydrogen atom model is Indicates δ +. FIG. 4B illustrates the contents indicated by the fields of the record 401-1 and the record 401-2.

  FIG. 5 is an explanatory diagram showing an example of the contents stored in the solvent arrangement plane data. The solvent arrangement surface data 501 stores information regarding the surface 112 covering the target molecule model 111. FIG. 5A shows an example of the storage contents of the solvent arrangement plane data 501. FIG. 5B illustrates the contents indicated by each field of the solvent arrangement plane data 501.

  The solvent arrangement plane data 501 stores each lattice point on the surface of the target molecule model 111 as one record. The solvent arrangement surface data 501 shown in FIG. 5A stores a record 501-1. Although the solvent arrangement plane data 501 is stored for each lattice point, for example, when it is desired to specify the position of the solvent molecule model 121 more finely, it may be stored for a point whose coordinates that do not become a lattice point have decimal numbers.

  The solvent arrangement plane data 501 includes four fields: lattice point coordinates, normal vector, electric potential, and electric charge of the nearest atomic model. The grid point coordinate field stores the coordinate values of grid points in the coordinate system in which all coordinates are integers. The normal vector field stores the value of the normal vector for the surface at the lattice point. In the potential field, the value of the potential at the lattice point is stored. The charge field of the nearest atom model stores the value of the charge of the atom model closest to the lattice point. The charge field of the nearest atomic model may store whether the charge of the atomic model closest to the lattice point is a positive charge or a negative charge.

For example, in the record 501-1, for the lattice point L (x _L , y _L , z _L ) on the surface 112, the normal vector is the vector N _L , the potential value is E _L , and the nearest atom It shows that the charge of the model is δ +.

FIG. 5B illustrates the contents indicated by each field of the record 501-1. In FIG. 5B, the atomic model closest to the lattice point (x _L , y _L , z _L ) is the hydrogen atom model H_ (2), and the charge of the hydrogen atom model H_ (2) is δ +. It shows that there is.

  FIG. 6 is an explanatory diagram showing an example of the storage contents of the solvent molecule setting data. The solvent molecule setting data 601 stores values relating to solvent molecules. FIG. 6A shows an example of the storage contents of the solvent molecule setting data 601. In FIG. 6B, the contents indicated by each field of the solvent molecule setting data 601 are illustrated.

  The solvent molecule setting data 601 stores a value related to the solvent molecule model as one record. The solvent molecule setting data 601 shown in FIG. 6A stores records 601-1 and 601-2. Thus, there may be a plurality of types of solvent molecule models.

  The solvent molecule setting data 601 includes five fields: solvent molecule model ID, cylinder data, dipole moment, addition candidate point, and atom model coordinates. Information for identifying the solvent molecule model 121 is stored in the solvent molecule model ID field. The cylinder data field stores information indicating the structure of the cylinder model 122 that covers the solvent molecule model 121. Specifically, the cylinder data field has two subfields: a radius field and a height field. In the radius field, the radius of the cylindrical model 122 is stored. In the height field, the height of the cylindrical model 122 is stored. Each component of the coordinate axis of the dipole moment of the solvent molecule model 121 is stored in the dipole moment field. If the solvent molecule model 121 is a model imitating a nonpolar molecule, an arbitrary direction vector is stored in the dipole moment field.

  In the addition candidate point field, position information of the addition candidate point set on the surface of the cylindrical model 122 based on the position of the center of gravity of the charge of the solvent molecule model 121 is stored. Specifically, if the solvent molecule model 121 is a model simulating a polar molecule, additional candidate points are set at the intersections or contact points between the negative charge centroid and the straight line passing through the positive charge centroid and the surface of the cylindrical model 122. The If the solvent molecule model 121 is a model imitating a nonpolar molecule, the intersection of a straight line passing through the center of charge and having the same direction as the arbitrary direction vector stored in the dipole moment field and the surface of the cylindrical model 122 Alternatively, additional candidate points are set at the contact points. In the atom model coordinate field, position information of each atom model in the solvent molecule model 121 is stored.

  For example, record 601-1 indicates that the solvent is water and the radius of the cylinder is 1.9 angstroms. In FIG. 6, angstrom is displayed as [A]. Subsequently, the record 601-1 indicates that the height of the cylinder is 3.6 [A] and the dipole moment is (0 debye, 0 debye, 1.85 debye). Hereinafter, Debye, which is one of the units representing the dipole moment, is indicated as [D] in FIG.

  Furthermore, in the record 601-1, there are two additional candidate points p1 and p2, the coordinates of p1 are (0, 0, 0), and the coordinates of p2 are (0, 0, 3.6). Indicates. Further, in the record 601-1, the position of the oxygen atom model is (0, 0, 1.4), the position of the first hydrogen atom model is (0.8, 0, 2.0), The position of the second hydrogen atom model is (−0.8, 0, 2.0). FIG. 6B shows the contents indicated by each field of the record 601-1. In FIG. 6B, p1 coincides with the origin. The origin may be at any position. Next, a functional configuration of the calculation support apparatus 101 using the user setting data 301, the atom information data 401, the solvent arrangement plane data 501 and the solvent molecule setting data 601 will be described with reference to FIG.

(Functional configuration of the calculation support apparatus 101)
Next, the functional configuration of the calculation support apparatus 101 will be described. FIG. 7 is a block diagram illustrating a functional configuration example of the calculation support apparatus. The calculation support apparatus 101 includes a potential calculation unit 701, a determination unit 702, an extraction unit 703, a setting unit 704, a position information calculation unit 705, and an output unit 706. The potential calculation unit 701 to the output unit 706 serving as the control unit realize the functions of the potential calculation unit 701 to the output unit 706 when the CPU 201 executes a program stored in the storage device. Specifically, the storage device is, for example, the ROM 202, the RAM 203, the magnetic disk 205, the optical disk 207, etc. shown in FIG. Alternatively, the functions of the potential calculation unit 701 to the output unit 706 may be realized by another CPU executing via the I / F 209.

  Further, the calculation support apparatus 101 can access user setting data 301, atom information data 401, solvent arrangement surface data 501, and solvent molecule setting data 601 as a storage unit. User setting data 301, atomic information data 401, solvent arrangement plane data 501, and solvent molecule setting data 601 are stored in a storage device such as the RAM 203, the magnetic disk 205, and the optical disk 207.

  The atomic information data 401 stores the charge value of each atomic model in the target molecule model 111 for each point of the point group set on the surface 112 covering the target molecule model 111 arranged on the spatial coordinates. For example, as shown in FIG. 4, the atom information data 401 stores that the carbon atom model that becomes C_ (1) has a charge δ−.

The solvent arrangement plane data 501 stores position information for each point of the point group set on the plane 112. For example, as illustrated in FIG. 5, the solvent arrangement plane data 501 stores that the position information of the lattice points on the plane 112 is (x _L , y _L , z _L ).

  Further, the solvent arrangement plane data 501 stores information for specifying the value of the charge of the atomic model closest to the point among the atomic models in the target molecule model 111 for each point of the point group on the plane 112. Also good. Information specifying the charge value of the closest atomic model includes, for example, position information of a point cloud on the surface 112, position information of each atomic model of the target molecule model 111, and charge value of each atomic model. Also good. Alternatively, the information for specifying the charge value of the closest atomic model may be the identification information of the closest atomic model and the charge value of each atomic model for each point of the point group on the surface 112. For example, as shown in FIG. 5, the solvent arrangement plane data 501 stores the charge value δ + of the nearest atomic model at the lattice point coordinate L.

In addition, the solvent arrangement plane data 501 may store information indicating the direction of a normal extending outside the surface 112 covering the target molecule model 111 at each point of the point group on the surface 112. The information indicating the direction of the normal is, for example, a normal vector. The information indicating the direction of the normal line may be a normal unit vector extending outside the surface 112. For example, as shown in FIG. 5, the solvent arrangement plane data 501 stores the normal vector N _L at the lattice point coordinate L.

  The solvent molecule setting data 601 stores position information of each atomic model in the solvent molecule model 121 when the solvent molecule model 121 is arranged on spatial coordinates. For example, as shown in FIG. 6, the solvent molecule setting data 601 stores oxygen atom models and positional information of two hydrogen atom models. Further, the solvent molecule setting data 601 stores position information of addition candidate points set on the surface covering the solvent molecule model 121 based on the position of the center of gravity of the charge of the solvent molecule model 121. For example, as illustrated in FIG. 6, the solvent molecule setting data 601 stores position information of addition candidate points p1 and p2.

  Further, the solvent molecule setting data 601 further includes the intersection or / and the position of the contact point between the straight line passing through the centroid of the negative charge of the solvent molecule model 121 and the centroid of the positive charge of the solvent molecule model 121 and the surface covering the solvent molecule model 121. Store information. Further, the solvent molecule setting data 601 may store information for specifying the positive / negative of the potential value at the intersection or / and the contact point based on the charge value of each atomic model in the solvent molecule model 121.

  The intersection or / and contact point of the straight line passing through the negative charge centroid of the solvent molecule model 121 and the positive charge centroid of the solvent molecule model 121 and the surface covering the solvent molecule model 121 is an addition candidate point. The intersection or / and the contact point between the straight line passing through the negative charge centroid of the solvent molecule model 121 and the positive charge centroid of the solvent molecule model 121 and the surface covering the solvent molecule model 121 is referred to as an addition candidate point. Further, the information for specifying the sign of the potential value at the additional candidate point is, for example, a dipole moment. The dipole moment indicates the direction in the molecule from the position of the negative charge centroid to the position of the positive charge centroid. Further, the information specifying the positive / negative of the potential value at the addition candidate point may be a vector indicating the direction from the position of the center of gravity of the positive charge toward the position of the center of gravity of the negative charge. For example, as shown in FIG. 6, the solvent molecule setting data 601 stores the position information of the addition candidate points p1 and p2 and the dipole moment.

  The potential calculation unit 701 refers to the atomic information data 401 and calculates a potential value at a point set on the surface 112. For example, the potential calculation unit 701 calculates the potential at each point by superposing the potentials generated by the charges of each atom in the target molecule model 111. Further, the potential calculation unit 701 may calculate the potential at each point using the calculation result of the molecular orbital calculation.

  In addition, when the determination unit 702 determines the arrangement point, the potential calculation unit 701 refers to the atomic information data 401 and the charge value of each atomic model in the solvent molecule model 121 for each point shown below, The potential value at the point may be calculated. Further, the points are points of a point group set on a surface covering the target molecule model 111 and the solvent molecule model 121 arranged at the arrangement point. The charge value of each atomic model in the solvent molecule model 121 may be included in the solvent molecule setting data 601, for example. Note that the calculated potential value is stored in a storage area such as the RAM 203, the magnetic disk 205, or the optical disk 207.

  The determination unit 702 combines the target molecule model 111 and the solvent molecule model 121 forming the solution model based on the potential value at the point calculated by the potential calculation unit 701 from the point group set on the surface 112. Determine the placement point. For example, the determination unit 702 may determine a point where the absolute value of the potential value is a local maximum value as the arrangement point.

  In addition, the determination unit 702 may determine, from the point group set on the surface 112, a point where the absolute value of the potential value at the point is the maximum as an arrangement point. For example, in the example of FIG. 1, the determination unit 702 determines, from the point group set on the surface 112, the point (1) having the maximum absolute value of the potential as the arrangement point.

  In addition, the determination unit 702 determines an arrangement point to which another solvent molecule model 121 is bonded based on the potential value at the point calculated by the potential calculation unit 701 from the remaining points extracted by the extraction unit 703. May be. The other solvent molecule model 121 forms a solution model with the target molecule model 111 and the solvent molecule model 121. Note that the solvent molecule model 121 and the other solvent molecule model 121 may be the same type of molecular model or different molecular models. For example, the determination unit 702 determines, from among the remaining points extracted by the extraction unit 703, the point where the absolute value of the potential value at the point is the maximum as the arrangement point to which the other solvent molecule model 121 is coupled.

  In addition, the determination unit 702 generates other solution models that form a solution model with the target molecule model 111 and the solvent molecule model 121 based on the value of the potential at the point calculated by the potential calculation unit 701 from the following point group. The arrangement point where the solvent molecule model 121 is bonded may be determined. The point group is a point group set on a surface covering the target molecule model 111 and the solvent molecule model 121 arranged at the arrangement point. The identification information of the points determined as the arrangement points is stored in a storage area such as the RAM 203, the magnetic disk 205, and the optical disk 207.

  When the extraction unit 703 determines the arrangement point, the extraction unit 703 projects the surface covering the solvent molecule model 121 onto the surface 112 from the point group, with the normal direction extending from the surface 112 at the arrangement point as the projection direction. The remaining points excluding the points included in the projection figure obtained by the above are extracted. Details will be described later with reference to FIG.

  Further, the extraction unit 703 may extract the remaining points excluding the points included in the enlarged graphic that is enlarged based on the distance from the center point of the projected graphic to the outline of the projected graphic with the projected graphic as the center. Good. The outline of the projected figure is a line indicating the outer contour of the projected figure. For example, if the projected figure is a circle, the extraction unit 703 extracts the remaining points excluding the points included in the enlarged figure enlarged by twice the radius. If the distance from the center of the projected figure to the outline is different, the extraction unit 703 enlarges the minimum distance from the center to the outline. The extracted point identification information is stored in a storage area such as the RAM 203, the magnetic disk 205, and the optical disk 207.

  The setting unit 704 sets one of the additional candidate points as an additional point based on the information specifying the positive / negative of the potential value at the determined arrangement point and the positive / negative of the potential value at the additional candidate point. For example, if the potential value at the arrangement point is negative, the setting unit 704 sets the additional candidate point where the potential is positive and the charge is negative as the additional point in the direction opposite to the direction indicated by the dipole moment. To do. If the potential value at the arrangement point is positive, the setting unit 704 sets an additional candidate point that is in the direction indicated by the dipole moment, has a negative potential, and has a positive charge, as the additional point. Note that a negative potential corresponds to a positive charge, and a positive potential corresponds to a negative charge.

  In addition, when the potential value at the determined arrangement point is 0, the setting unit 704 specifies whether the charge value of the atomic model closest to the determined arrangement point is positive or negative and the potential value at the additional candidate point is positive or negative. Based on the information, any of the additional candidate points may be set as the additional point. For example, if the charge value of the atomic model closest to the arrangement point is positive, the setting unit 704 is in the opposite direction to the direction indicated by the dipole moment, the potential is positive, and the additional candidate point where the charge is negative. Is set as an additional point. If the charge value of the atomic model closest to the arrangement point is negative, the setting unit 704 is in the direction indicated by the dipole moment, the potential is negative, and the additional candidate point whose charge is positive is the additional point. Set. The identification information of the additional candidate points set as the additional points is stored in a storage area such as the RAM 203, the magnetic disk 205, and the optical disk 207.

  The position information calculation unit 705 sets the position of the additional point as the position of the arrangement point based on the position information of the determined arrangement point, the position information of the addition point, and the position information of each atomic model in the solvent molecule model 121. The position information of each atomic model in the solvent molecule model 121 when set is calculated. A specific calculation method will be described later with reference to FIG.

  Further, the position information calculation unit 705 determines the position of any point based on the position information of the arrangement point, the position information of any point, and the position information of each atomic model in the solvent molecule model 121. Position information of each atomic model in the solvent molecule model 121 is calculated.

  Further, the position information calculation unit 705 calculates position information from the addition point in each atomic model in the solvent molecule model 121 based on the position information of the addition point and the position information of each atom model in the solvent molecule model 121. May be.

  In addition, the position information calculation unit 705 sets the position of the additional point as the position of the arrangement point when rotated until the direction of the normal line at the arrangement point and the direction from the positive charge centroid to the negative charge centroid overlap. In this case, position information of each atomic model in the solvent molecule model 121 may be calculated. At this time, if the potential value of the additional point is negative, the positional information calculation unit 705 determines the positional information of the determined arrangement point, the positional information of the additional point stored in the storage unit, and the solvent molecule model 121. Based on the position information from the additional point in each atomic model, calculation is performed with the additional point as the center. A specific calculation method will be described later with reference to FIG.

  Further, the position information calculation unit 705 sets the position of the additional point as the position of the placement point when rotated until the direction of the normal line at the placement point and the direction from the negative charge centroid to the positive charge centroid overlap. The position information of each atomic model in the solvent molecule model 121 when set may be calculated. At this time, when the potential value of the additional point is positive, the positional information calculation unit 705 determines the positional information of the determined arrangement point, the positional information of the additional point stored in the storage unit, and the solvent molecule model 121. Based on the position information from the additional point in each atomic model, the calculation is performed with the additional point as the center. The calculated position information is stored in a storage area such as the RAM 203, the magnetic disk 205, or the optical disk 207.

  The output unit 706 outputs the calculated position information of each atomic model in the solvent molecule model 121. Examples of the output format include display on the display 208 and transmission to an external device using the I / F 209. The output unit 706 may store the output result in a storage area such as the RAM 203, the magnetic disk 205, and the optical disk 207.

  FIG. 8 is an explanatory view showing an arrangement example of a solvent molecule model. It is assumed that the target molecule model 111 is in the dielectric model 110 imitating a uniformly polarized dielectric. First, the calculation support apparatus 101 performs molecular orbital calculation on the target molecular model 111 assumed to be in a vacuum, and generates solvent arrangement plane data 501 from the calculation result. As a specific method for generating the solvent arrangement plane data 501, for example, the calculation support apparatus 101 acquires the isosurface information of the electron density obtained from the calculation result of the molecular orbital calculation using the surface covering the target molecule model 111. Specifically, the calculation support apparatus 101 obtains a set of lattice points closest to an electron density value of 0.001. A set of lattice points becomes a lattice point where the solvent molecule model 121 can be arranged. Next, for each lattice point, the calculation support apparatus 101 converts the lattice point spatial coordinates, the molecular surface normal vector at the lattice point, the potential value at the lattice point obtained from the calculation result, and the lattice point obtained from the calculation result. The charge of the nearest atom model is generated as the solvent arrangement plane data 501.

  Further, the calculation support apparatus 101 reads the solvent molecule setting data 601 and generates the cylindrical model 122. As a specific method for generating the cylinder model 122, for example, the calculation support apparatus 101 sets the radius and height of a cylinder covering a molecule obtained from the calculation result of the molecular orbit calculation performed on the solvent molecule model 121. . At this time, the calculation support apparatus 101 sets the direction of the cylinder on the space coordinates to the direction of the dipole moment obtained as a result of the molecular orbital calculation.

  The calculation support apparatus 101 sets the center of the terminal circle of the cylindrical model 122 as an additional candidate point. Furthermore, the calculation support apparatus 101 sets the spatial coordinates of each atomic model of the solvent molecule model 121 as relative coordinates from any of the additional candidate points. Further, for the solvent molecule model 121, the calculation support apparatus 101 stores a record for each solvent molecule model 121 and reads a plurality of records corresponding to the corresponding solvent molecule model 121 from the solvent molecule setting data 601. The cylindrical model 122 is generated. In the example of FIG. 8, it is assumed that the cylinder model 122 is the water molecule indicated by the record 601-1.

  Next, the calculation support apparatus 101 determines a grid point with the maximum absolute value of the potential value as a placement point of the cylindrical model 122 from grid points where the cylindrical model 122 can be placed. In FIG. 8, the difference in potential value in the surface 112 is shown by hatching. The value of the potential represented by the hatch is the same as that in FIG. For example, the calculation support apparatus 101 determines the grid point (1) having the maximum absolute value of the potential value from among the grid points (1) to (5) illustrated in FIG. To do. The value of the potential of the grid point (1) is negative, the coordinates of the grid point (1) are, for example, (100, 10, 50), and a method for expressing the direction perpendicular to the plane 112 of the grid point (1). Assume that the line vector is (1, 0, 0).

  Subsequently, the calculation support apparatus 101 sets one of the additional candidate points of the two additional candidate points of the cylindrical model 122-1 as an additional point that is coupled to the lattice point (1). Since the potential value of the grid point (1) is negative and the charge is positive, the calculation support apparatus 101 sets the additional candidate point p1 on the negative charge side as an additional point that is coupled to the grid point (1). . Next, the calculation support apparatus 101 sets the coordinates of the additional point p1 after the arrangement of the cylindrical model 122-1 to the coordinates (100, 10, 50) of the lattice point (1). Hereinafter, “after arrangement of the cylindrical model 122-1” is simply referred to as “after arrangement”.

  Further, the calculation support apparatus 101 uses the coordinates of the arrangement point, the coordinates of p1 set as the additional point, and the position information of each atomic model of the solvent molecule model 121 to each of the solvent molecule models 121 after the arrangement. Calculate the position information of the atomic model. Specifically, the calculation support apparatus 101 calculates position information of each atom of the solvent molecule model 121 after the arrangement using the following formula (1).

  Position information of each atom of the solvent molecule model 121 after arrangement = coordinate of arrangement point−coordinate of additional point + position information of each atom of the solvent molecule model 121 (1)

  Formula (1) is a formula that translates the positional information of each atom of the solvent molecule model 121 in accordance with the value obtained by moving the additional point. For example, the calculation support apparatus 101 calculates the coordinates of the oxygen atom model of the solvent molecule model 121 after the arrangement using the equation (1) as follows.

Coordinates of oxygen atom model of solvent molecule model 121 after arrangement = coordinates of arrangement point−coordinates of p1 + position information of oxygen atom model⇔coordinates of oxygen atom model of solvent molecule model 121 after arrangement = (100, 10, 50 )-(0,0,0) + (0,0,1.4)
Coordinates of the oxygen atom model after ⇔ arrangement = (100, 10, 51.4)

  In addition, the calculation support apparatus 101 determines the direction of the normal vector perpendicular to the surface 112 at the lattice point (1), the direction of the dipole moment of the solvent molecule model 121, and the position information of each atom as a result of the expression (1). May be used to calculate the positional information of each atomic model of the solvent molecule model 121 after placement. Specifically, the calculation support apparatus 101 calculates position information of each atomic model of the solvent molecule model 121 after the arrangement using the following equation (2).

  Position information of each atom of the solvent molecule model 121 after placement = coordinate of placement point + rotation matrix. (Position information of each atom as a result of the formula (1) −coordinate of additional point after placement) (2)

The rotation matrix is a matrix that performs rotation on spatial coordinates. Here, since the potential at the additional point becomes positive and the charge becomes negative, rotation is performed until the direction of the dipole moment is aligned with the direction of the normal vector. For example, a rotation matrix R _y (θ) for rotating the Z axis around the Y axis by θ in the X axis direction is expressed by the following equation (3).

  In the example of the lattice point (1), since the normal vector is (1, 0, 0) and the dipole moment is (0, 0, 1.85), the Z axis is set to the X axis around the Y axis. It will rotate 90 degrees in the direction. In addition, in order to obtain | require the rotation angle of two vectors, it can obtain | require by calculating the inner product of two vectors. For example, the calculation support apparatus 101 calculates the coordinates of the oxygen atom model of the solvent molecule model 121 after the arrangement using the equations (2) and (3) as follows.

Coordinate of oxygen atom model after arrangement = coordinate of arrangement point + R _y (90 degrees) · (position information of oxygen atom as a result of equation (1) −coordinate of additional point p1 after arrangement)
Coordinates of oxygen atom model after arrangement of （= (100, 10, 50) + R _y (90 degrees) · ((100, 10, 51.4) − (100, 10, 50))
Coordinates of oxygen atom model after ⇔ arrangement = (100, 10, 50) + R _y (90 degrees) · (0, 0, 1.4)
Coordinates of oxygen atom model after ⇔ arrangement = (100, 10, 50) + (1.4, 0, 0) = (101.4, 10, 50)

  The calculation support apparatus 101 also calculates position information for other atomic models in the solvent molecule model 121. Thus, the calculation support apparatus 101 arranges the cylindrical model 122-1 by executing the expressions (1) and (2). Subsequently, the calculation support apparatus 101 arranges a second cylindrical model 122-2. For example, the calculation support apparatus 101 determines the grid point (2) in which the absolute value of the potential value is the largest next to the grid point (1) as the arrangement point of the cylindrical model 122-2. It is assumed that the value of the potential at the lattice point (2) is positive.

  Subsequently, the calculation support apparatus 101 sets one of the additional candidate points of the two additional candidate points of the cylindrical model 122-2 as an additional point that is coupled to the grid point (2). Since the potential value of the grid point (2) is positive, the calculation support apparatus 101 sets the additional candidate point p2 on the positive charge side as an additional point that is coupled to the grid point (2). Hereinafter, the calculation support apparatus 101 calculates the position of each atomic model of the solvent molecule model in the cylindrical model 122-2 using the equations (1) and (2).

  Subsequently, the calculation support apparatus 101 determines, as the arrangement point of the cylindrical model 122-3, the lattice point (3) in which the absolute value of the potential value is the largest after the lattice point (1) and the lattice point (2). Then, the cylindrical model 122-3 is arranged. Similarly, the calculation support apparatus 101 determines, as the arrangement point of the cylindrical model 122-4, the lattice point (4) in which the absolute value of the potential value becomes the maximum next to the lattice point (1) to the lattice point (3). Then, the cylindrical model 122-4 is arranged.

  Next, the calculation support apparatus 101 determines, as the arrangement point of the cylindrical model 122-5, the lattice point (5) in which the absolute value of the potential value is the second largest after the lattice points (1) to (4). To do. It is assumed that the value of the potential at the lattice point (5) is zero. Subsequently, the calculation support apparatus 101 sets one of the additional candidate points of the two additional candidate points of the cylindrical model 122-5 as an additional point that is coupled to the lattice point (5). Since the value of the potential of the lattice point (5) is 0, the calculation support apparatus 101 sets an additional point based on the sign of the charge of the atomic model closest to the lattice point (5). In the example of FIG. 8, since the charge of the atomic model closest to the lattice point (5) is positive, the additional candidate point p1 on the negative charge side is set as an additional point coupled to the lattice point (5). Hereinafter, the calculation support apparatus 101 calculates the position of each atomic model of the solvent molecule model 121 in the cylindrical model 122-5 using the equations (1) and (2).

  FIG. 9 is an explanatory diagram showing an example of a method of extracting lattice points after the solvent molecule model is arranged. In FIG. 9, after determining the arrangement of the cylindrical model 122 including the solvent molecule model 121, a process for extracting a point at which the next cylindrical model 122 can be arranged will be described. On the surface 112, there are lattice points p11 to p17, p21 to p27, and p31. Then, it is assumed that the calculation support apparatus 101 determines p31 as the arrangement point of the cylindrical model 122-1.

  Subsequently, the calculation support apparatus 101 obtains the remainder excluding the points included in the projection figure 901 obtained by projecting the surface covering the cylindrical model 122-1 onto the surface 112 in the direction perpendicular to the surface 112 at the lattice point p31. Extract points. Further, the calculation support apparatus 101 removes the projection graphic 901 from the points included in the enlarged graphic 902 that is enlarged based on the distance from the center point of the projected graphic 901 to the outline of the projected graphic 901 centering on the arrangement point The points may be extracted. For example, the calculation support apparatus 101 extracts the remaining points excluding the points included in the enlarged figure 902 obtained by enlarging the projected figure 901 by twice the radius r of the cylindrical model 122-1.

  In the example of FIG. 9, the calculation support apparatus 101 includes p14 included in the enlarged figure 902 obtained by enlarging the projected figure 901 by twice the radius r of the projected figure 901 among the point groups p11 to p17, p21 to p27, and p31. , The remaining points other than p23 to p25 are extracted.

  FIG. 10 is an explanatory diagram showing an example of the arrangement of the solvent molecule model in the second layer. FIG. 10 shows an example of processing after the processing shown in FIGS. 8 and 9 is performed and there are no grid points that can be arranged. At this time, the calculation support apparatus 101 uses the target molecule model 111 and the solvent molecule models 121-1 to 121-5 as new target molecule models, and provides a solvent arrangement that becomes information on the surface 302 covering the new target molecule model. Surface data 501 is generated.

  As a method for generating the solvent arrangement plane data 501 corresponding to the new target molecule model, for example, the calculation support apparatus 101 performs molecular orbital calculation on the new target molecule model, and the electron density equivalent value obtained from the calculation result The solvent arrangement surface data 501 may be generated from the surface information. Further, the calculation support apparatus 101 generates a set of lattice points closest to the surface 302 from the van der Waals radii of each atomic model of the new target molecular model, and a solvent for the set of lattice points closest to the surface 302. The arrangement plane data 501 may be generated.

  Next, the calculation support apparatus 101 determines a lattice point (6) having the maximum absolute value of the potential value from the point group on the surface 302 as an additional point of the cylindrical model 122-6, and the cylindrical model. 122-6 is arranged.

  Next, FIG. 11 and FIG. 12 show flowcharts of the calculation support apparatus 101 that performs the operation examples shown in FIGS.

  FIG. 11 is a flowchart illustrating an example of the arrangement processing procedure. The placement process is a process for placing the solvent molecule model on the target molecule model. The calculation support apparatus 101 sets the target molecule model 111 (step S1101). Next, the calculation support apparatus 101 sets the number of solvent arrangements by a user operation (step S1102). Subsequently, the calculation support apparatus 101 reads the solvent molecule setting data 601 and generates the cylindrical model 122 (step S1103).

  Next, the calculation support apparatus 101 executes molecular orbital calculation for the target molecule model 111 (step S1104). Subsequently, the calculation support apparatus 101 generates the solvent arrangement surface data 501 from the calculation result of the molecular orbital calculation (step S1105). Next, the calculation support apparatus 101 performs additional point setting processing (step S1106). Details of the additional point setting process will be described later with reference to FIG.

  After executing the process of step S1106, the calculation support apparatus 101 checks the value of the potential at the additional point (step S1107). When the potential value of the additional point is negative (step S1107: negative), the calculation support apparatus 101 reverses the direction of the normal vector at the arrangement point around the additional point and the dipole moment of the solvent molecule model 121. The cylindrical model 122 is rotated until the two overlap, and the position information of each atomic model of the solvent molecule model 121 is calculated (step S1108). When the potential value of the additional point is positive (step S1107: positive), the calculation support apparatus 101 determines the direction of the normal vector at the arrangement point around the additional point and the dipole moment of the solvent molecule model 121. The cylindrical model 122 is rotated until the directions overlap, and the position information of each atomic model of the solvent molecule model 121 is calculated (step S1109).

  After execution of step S1108 or step S1109, the calculation support apparatus 101 includes lattice points included in the enlarged figure 902 of the projected figure 901 obtained by projecting the solvent molecule model 121 whose position is determined in the direction opposite to the normal vector. Are deleted from the lattice points that can be arranged (step S1110). Next, the calculation support apparatus 101 determines whether or not the number of arranged solvent molecule models matches the number of arranged solvent molecule models (step S1111). If they do not match (step S1111: No), the calculation support apparatus 101 sets the target molecule model and the arranged solvent molecule model as a new target molecule model (step S1112). Next, the calculation support apparatus 101 proceeds to the process of step S1104. In step S1104 after step S1112, the calculation support apparatus 101 performs molecular orbital calculation on the new target molecule model.

  If they match (step S1111: Yes), the calculation support apparatus 101 outputs position information of each atomic model of the arranged solvent molecule model 121 (step S1113). After the process of step S1113 is completed, the calculation support apparatus 101 ends the arrangement process. By executing the placement process, the calculation support apparatus 101 places the solvent molecule model at a position where interaction is likely to occur, so that the calculation accuracy of the physical property value can be improved.

  When there are two or more types of solvent molecule models in the solution model, the calculation support apparatus 101 selects a random one of the two or more types of solvent molecule models as the target solvent molecule model in steps S1106 to S1110. The solvent molecule model selected in (1) may be used. Alternatively, the calculation support apparatus 101 may select a target solvent molecule model in order from a solvent molecule model having a large dipole moment among two or more types of solvent molecule models. Or the calculation assistance apparatus 101 may select the solvent molecule model used as an object in order from the solvent molecule model with a large mixing ratio in a solution model among two or more types of solvent molecule models.

  FIG. 12 is a flowchart illustrating an example of an additional point setting process procedure. The additional point setting process is a process of setting an additional point that is coupled to the surface 112 covering the target molecule model 111 among the additional candidate points of the cylindrical model 122.

  The calculation support apparatus 101 determines an arrangement point that maximizes the absolute value of the electrostatic potential from among the arrangementable lattice points (step S1201). Next, the calculation support apparatus 101 determines whether the magnitude of the dipole moment is 0 (step S1202). When the magnitude of the dipole moment is 0 (step S1202: Yes), since it is a nonpolar molecule, the calculation support apparatus 101 sets an additional candidate point of the cylindrical model 122 as an additional point (step S1203).

  When the magnitude of the dipole moment is not 0 (step S1202: No), the calculation support apparatus 101 checks the value of the potential at the determined arrangement point (step S1204). When the potential value is 0 (step S1204: 0), the calculation support apparatus 101 confirms the charge value of the atomic model closest to the determined arrangement point (step S1205).

  When the potential value is negative (step S1204: negative) or the charge value is positive (step S1205: positive), the calculation support apparatus 101 uses the dipole among the additional candidate points of the cylindrical model 122. An additional candidate point in a direction opposite to the direction indicated by the moment is set as an additional point (step S1206). When the potential value is positive (step S1204: positive) or the charge value is negative (step S1205: negative), the calculation support apparatus 101 includes the additional candidate points of the cylindrical model 122. An additional candidate point in the direction indicated by the dipole moment is set as an additional point (step S1207).

  After completion of any one of steps S1203, S1206, and S1207, the calculation support apparatus 101 sets the position of the additional point of the selected solvent molecule model as the position of the arrangement point (step S1208). After the process of step S1208 ends, the calculation support apparatus 101 ends the additional point setting process. By executing the additional point setting process, the calculation support apparatus 101 can select an additional point suitable for the potential value at the arrangement point.

  As described above, according to the calculation support apparatus 101, when calculating the physical property value of the target molecule in the solvent, the solvent molecule model 121 is used by using the potential value of each point on the surface 112 covering the target molecule model 111. Determine the placement point to place. As a result, the solvent molecule model 121 can be arranged at a position where the interaction is likely to occur. Therefore, the calculation support apparatus 101 determines the calculation accuracy of the physical property value that is the calculation result of the molecular orbital calculation using the arrangement result by the user's experience. This can be improved as compared with the case of being arranged based on the above.

  Further, according to the calculation support apparatus 101, the position of the additional point of the solvent molecule model 121 may be set to the position of the arrangement point, and the position information of each atomic model of the solvent molecule model 121 may be calculated. Thereby, since the calculation support apparatus 101 can acquire the position of the atomic model at a position where the interaction is likely to occur, the calculation accuracy can be improved. In addition, the calculation support apparatus 101 can display each atomic model of the solvent molecule model 121 arranged at a position where interaction is likely to occur, for example, on the display 208. Also, by calculating the position of each atomic model and arranging the solvent molecule model 121, the user does not have to perform a process of moving to the coordinates at which each solvent molecule is actually arranged, and is free from complicated operations. .

  Further, according to the calculation support apparatus 101, based on the sign of the potential value of the arrangement point among the additional candidate points on the positive charge side and the additional candidate points on the negative charge side set by the center of charge of the solvent molecule model 121. Thus, an additional point that binds to the target molecule model 111 may be set. Thereby, since the calculation support apparatus 101 can arrange | position the upper and lower sides of the solvent molecule | numerator model 121 in the direction actually couple | bonded, it can improve the calculation accuracy of a physical-property value.

  Further, according to the calculation support apparatus 101, when the potential value of the arrangement point is 0, an additional point that binds to the target molecule model 111 is set based on the sign of the charge of the atomic model closest to the arrangement point. May be. Thereby, since the calculation assistance apparatus 101 can arrange | position the direction of the solvent molecule | numerator model 121 in the direction actually couple | bonded, it can improve the calculation accuracy of a physical-property value. Further, by arranging the solvent molecule model 121 in consideration of the direction of the solvent molecule model 121, it is not necessary to perform the process of adjusting the direction after the user has moved to the coordinates where the solvent molecules are actually to be arranged. Freed from messy operations.

  Further, according to the calculation support apparatus 101, when the potential value of the additional point is negative, when the rotation is performed with the additional point as the center until the normal direction at the arrangement point and the opposite direction of the dipole moment overlap. Position information of each atomic model in the solvent molecule model 121 may be calculated. As a specific example, the solvent molecule model 121-2 is arranged at the lattice point (2) where the potential of the arrangement point is positive in FIG. At this time, the potential at the addition point of the solvent molecule model 121-2 is negative. Thereby, since the calculation support apparatus 101 can arrange | position the inclination of the solvent molecule | numerator model 121 in the direction actually couple | bonded, it can improve the calculation precision of a physical-property value.

  Further, according to the calculation support apparatus 101, when the potential value of the additional point is positive, the solvent when rotated until the direction of the normal line and the direction of the dipole moment at the arrangement point overlap with each other about the additional point. The position information of each atomic model in the molecular model 121 may be calculated. As a specific example, in FIG. 8, the solvent molecule model 121-1 is arranged at the lattice point (1) where the potential at the arrangement point is negative. At this time, the potential at the addition point of the solvent molecule model 121-1 is positive. Thereby, since the calculation support apparatus 101 can arrange | position the inclination of the solvent molecule | numerator model 121 in the direction actually couple | bonded, it can improve the calculation precision of a physical-property value.

  As described above, the calculation support apparatus 101 arranges the solvent molecule model 121 in consideration of the direction of the solvent molecule model 121, so that the user moves to the coordinates where the solvent molecules are actually arranged and aligns the directions. This frees you from complicated operations. Specifically, when there are n positions that can be arranged, the user has moved the solvent molecule model 121 to an appropriate position and adjusted the rotation in an appropriate direction. This involved complicated operations. The calculation support apparatus 101 according to the present embodiment can release the user from such a complicated operation.

  Further, according to the calculation support apparatus 101, a point at which the absolute value of the potential value on the surface 112 covering the target molecule model 111 is maximized may be determined as the arrangement point. Thereby, the calculation support apparatus 101 can arrange | position the solvent molecule | numerator model 121 in the location where interaction is the easiest.

  Further, according to the calculation support apparatus 101, when the arrangement point is determined, the projection figure obtained by projecting the cylindrical model 122 onto the surface 112 with the direction of the normal line extending inside the surface 112 at the arrangement point as the projection direction. The remaining points excluding the points included in 901 may be extracted. As a result, the calculation support apparatus 101 can determine the arrangement point of the solvent molecule model 121 to be arranged next at a position where it can be actually arranged without overlapping the already arranged solvent molecule model 121. It is possible to calculate a physical property value in a state where the property is high.

  Further, according to the calculation support apparatus 101, the remaining figure excluding the points included in the enlarged figure 902 that is enlarged based on the distance from the center point of the projected figure 901 to the outline of the projected figure 901 with the projected figure 901 as the center. The points may be extracted. For example, when the cylinder model 122 is arranged, the point at which the center of another cylinder model 122 can be arranged is outside the circle twice the radius of the cylinder model 122 from the center of the cylinder model 122. In this way, by extracting the remaining points excluding the enlarged figure, the calculation support apparatus 101 can place the next solvent molecule model 121 at a point where it can actually be placed. It is possible to calculate a physical property value in a state where the property is high.

  Further, according to the calculation support apparatus 101, when the arrangement point is determined, the potential value is calculated using the target molecule model 111 and the solvent molecule model 121 as the new target molecule model, and the new target molecule model is covered. In addition, the arrangement point to which the new solvent molecule model 121 is bonded may be determined. Thereby, since the calculation support apparatus 101 can detect the point where the interaction is most likely to occur on the surface covering the new target molecule model, the calculation accuracy of the physical property value can be further improved.

  The calculation support method described in this embodiment can be realized by executing a program prepared in advance on a computer such as a personal computer or a workstation. The calculation support program is recorded on a computer-readable recording medium such as a hard disk, a flexible disk, a CD-ROM, an MO, and a DVD, and is executed by being read from the recording medium by the computer. The calculation support program may be distributed via a network such as the Internet.

  The following additional notes are disclosed with respect to the embodiment described above.

(Supplementary note 1)
For each point of the point group set on the surface covering the first molecular model arranged on the spatial coordinates, refer to the storage unit that stores the charge value of each atomic model in the first molecular model , Calculate the potential value at the point,
From the point group, based on the value of the potential at the calculated point, determine a placement point where the first molecular model and a second molecular model that forms a solution model are combined.
A calculation support program characterized by causing processing to be executed.

(Additional remark 2) The said memory | storage part is the position information for every point of the said point group, and the position of each atomic model in the said 2nd molecular model when arrange | positioning the said 2nd molecular model on the said space coordinate Information and the position information of the additional point set based on the position of the center of gravity of the charge of the second molecular model on the surface covering the second molecular model,
In the computer,
Based on the position information of the determined arrangement point, the position information of the additional point stored in the storage unit, and the position information of each atomic model in the second molecular model, the position of the additional point is determined. Calculating position information of each atomic model in the second molecular model when set to the position of the arrangement point;
Outputting positional information of each atomic model in the calculated second molecular model;
The calculation support program according to appendix 1, wherein the processing is executed.

(Additional remark 3) The said memory | storage part is further the intersection of the straight line which passes through the gravity center of the negative charge of the said 2nd molecular model, and the gravity center of the positive charge of the said 2nd molecular model, and the surface which covers the said 2nd molecular model Or / and the position information of the contact and the information specifying the positive / negative of the potential value at the intersection or / and the contact based on the charge value of each atomic model in the second molecular model,
In the computer,
Based on the determined positive / negative of the potential value at the arrangement point and the information specifying the positive / negative of the potential value at the intersection or / and the contact point, any one of the intersection point and / or the contact point is added. Execute the process to set the point,
The process of calculating the position information of each atomic model in the second molecular model is
Based on the position information of the arrangement point, the position information of any one of the points stored in the storage unit, and the position information of each atomic model in the second molecular model, The calculation support program according to appendix 2, wherein the position information of each atomic model in the second molecular model when the position is set to the position of the arrangement point is calculated.

(Additional remark 4) The said memory | storage part further memorize | stored the information which pinpoints the value of the electric charge of the atomic model nearest to the said point among each atomic model in the said 1st molecular model for every point of the said point group. And
The setting process is as follows:
When the value of the potential at the determined arrangement point is 0, the information specifying the positive / negative of the charge value of the atomic model closest to the determined arrangement point and the positive / negative of the potential value at the intersection or / and contact point The calculation support program according to attachment 3, wherein any one of the intersection and / or the contact point is set as the additional point based on the above.

(Additional remark 5) The said memory | storage part has further memorize | stored the information showing the direction of the normal line extended on the outer side of the surface which covers the said 1st molecular model in the said point for every point of the said point group,
In the computer,
A process of calculating position information from the additional point in each atomic model in the second molecular model based on the positional information of the additional point and the positional information of each atomic model in the second molecular model. Let it run
The process of calculating the position information of each atomic model in the second molecular model is
When the potential value of the set additional point is negative, the position information of the determined arrangement point, the position information of the additional point stored in the storage unit, and the calculated second molecular model Based on the position information from the additional point in each atomic model, the direction of the normal line at the arrangement point and the direction from the positive charge centroid to the negative charge centroid overlap with the additional point as a center. Appendix 3 or 4, wherein the position information of each atomic model in the second molecular model is calculated when the position of the additional point is set to the position of the arrangement point when rotated to The calculation support program described.

(Additional remark 6) The said memory | storage part has further memorize | stored the information showing the direction of the normal line extended on the outer side of the surface which covers the said 1st molecular model in the said point for every point of the said point group,
In the computer,
A process of calculating position information from the additional point in each atomic model in the second molecular model based on the positional information of the additional point and the positional information of each atomic model in the second molecular model. Let it run
The process of calculating the position information of each atomic model in the second molecular model is
When the potential value of the set additional point is positive, the position information of the determined arrangement point, the position information of the additional point stored in the storage unit, and the calculated second molecular model Based on the position information from the additional point in each atomic model, the direction of the normal line at the arrangement point and the direction from the negative charge centroid to the positive charge centroid overlap with the additional point as a center. Appendix 3 or 4, wherein the position information of each atomic model in the second molecular model is calculated when the position of the additional point is set to the position of the arrangement point when rotated to The calculation support program described.

(Supplementary note 7)
The calculation support program according to any one of appendices 1 to 6, wherein a point at which the absolute value of the potential value at the point is maximum is determined as the arrangement point from the point group. .

(Supplementary note 8)
When the arrangement point is determined, a surface that covers the second molecular model from the group of points, with a normal direction extending inside the surface that covers the first molecular model at the arrangement point as a projection direction To extract the remaining points excluding the points included in the projection figure obtained by projecting onto the surface covering the first molecular model,
Based on the calculated value of the potential at the point, the first molecular model, the second molecular model, and the third molecular model forming the solution model are extracted from the extracted remaining points. Determine placement points to be joined,
The calculation support program according to any one of appendices 1 to 7, wherein the program is executed.

(Supplementary note 9) The extraction process is
When the arrangement point is determined, a surface that covers the second molecular model from the group of points, with a normal direction extending inside the surface that covers the first molecular model at the arrangement point as a projection direction To a magnified figure obtained by projecting a projected figure obtained by projecting the first figure onto the surface covering the first molecular model based on the distance from the center point of the projected figure to the outline of the projected figure with the arrangement point as the center The calculation support program according to appendix 8, wherein the remaining points excluding the included points are extracted.

(Supplementary Note 10) In the computer,
When the arrangement point is determined, for each point of the point group set on the surface covering the first molecule model and the second molecule model arranged at the arrangement point, With reference to the storage unit storing the charge value of each atomic model and the charge value of each atomic model in the second molecular model, the value of the potential at the point is calculated,
Based on the value of the potential at the point calculated from the point group set on the surface covering the first molecular model and the second molecular model arranged at the arrangement point, the first molecular model Determining an arrangement point at which a molecular model and the second molecular model and a third molecular model forming the solution model are combined;
The calculation support program according to any one of appendices 1 to 9, wherein the program is executed.

(Additional remark 11) The memory | storage part which memorize | stores the value of the electric charge of each atomic model in the said 1st molecular model for every point of the point group set to the surface which covers the 1st molecular model arrange | positioned on a space coordinate , A potential calculation unit that calculates the value of the potential at the point; and
Based on the value of the potential at the point calculated by the potential calculation unit, an arrangement point where the first molecular model and the second molecular model forming the solution model are combined is determined from the point group. A decision unit to
A calculation support apparatus characterized by comprising:

(Supplementary note 12)
For each point of the point group set on the surface covering the first molecular model arranged on the spatial coordinates, refer to the storage unit that stores the charge value of each atomic model in the first molecular model , Calculate the potential value at the point,
From the point group, based on the value of the potential at the calculated point, determine a placement point where the first molecular model and a second molecular model that forms a solution model are combined.
A calculation support method characterized by executing processing.

DESCRIPTION OF SYMBOLS 101 Calculation support apparatus 111 Object molecule model 112 Surface 121 Solvent molecule model 701 Electric potential calculation part 702 Determination part 703 Extraction part 704 Setting part 705 Position information calculation part 706 Output part

Claims (11)

On the computer,
For each point of the point group set on the surface covering the first molecular model arranged on the spatial coordinates, refer to the storage unit that stores the charge value of each atomic model in the first molecular model , Calculate the potential value at the point,
From the point group, based on the value of the potential at the calculated point, determine a placement point where the first molecular model and a second molecular model that forms a solution model are combined.
A calculation support program characterized by causing processing to be executed. The storage unit includes positional information for each point of the point group, positional information of each atomic model in the second molecular model when the second molecular model is arranged on the spatial coordinates, The position information of the additional point set based on the position of the center of gravity of the charge of the second molecular model is stored on the surface covering the second molecular model,
In the computer,
Based on the position information of the determined arrangement point, the position information of the additional point stored in the storage unit, and the position information of each atomic model in the second molecular model, the position of the additional point is determined. Calculating position information of each atomic model in the second molecular model when set to the position of the arrangement point;
Outputting positional information of each atomic model in the calculated second molecular model;
The calculation support program according to claim 1, wherein the calculation is executed. The storage unit further includes an intersection or / and a contact point between a negative charge centroid of the second molecular model and a straight line passing through the positive charge centroid of the second molecular model and a surface covering the second molecular model. And the information specifying the positive / negative of the potential value at the intersection or / and contact point based on the charge value of each atomic model in the second molecular model,
In the computer,
Based on the determined positive / negative of the potential value at the arrangement point and the information specifying the positive / negative of the potential value at the intersection or / and the contact point, any one of the intersection point and / or the contact point is added. Execute the process to set the point,
The process of calculating the position information of each atomic model in the second molecular model is
Based on the position information of the arrangement point, the position information of any one of the points stored in the storage unit, and the position information of each atomic model in the second molecular model, The calculation support program according to claim 2, wherein position information of each atomic model in the second molecular model when the position is set to the position of the arrangement point is calculated. The storage unit further stores, for each point of the point group, information for specifying a charge value of an atomic model closest to the point among the atomic models in the first molecular model,
The setting process is as follows:
When the value of the potential at the determined arrangement point is 0, the information specifying the positive / negative of the charge value of the atomic model closest to the determined arrangement point and the positive / negative of the potential value at the intersection or / and contact point 4. The calculation support program according to claim 3, wherein any one of the intersection point and / or the contact point is set as the additional point based on the above. The storage unit further stores, for each point of the point group, information indicating the direction of a normal extending outside the surface covering the first molecular model at the point,
In the computer,
A process of calculating position information from the additional point in each atomic model in the second molecular model based on the positional information of the additional point and the positional information of each atomic model in the second molecular model. Let it run
The process of calculating the position information of each atomic model in the second molecular model is
When the potential value of the set additional point is negative, the position information of the determined arrangement point, the position information of the additional point stored in the storage unit, and the calculated second molecular model Based on the position information from the additional point in each atomic model, the direction of the normal line at the arrangement point and the direction from the positive charge centroid to the negative charge centroid overlap with the additional point as a center. 5. The position information of each atomic model in the second molecular model is calculated when the position of the additional point is set to the position of the arrangement point when the position is rotated to 5. The calculation support program described in 1. The storage unit further stores, for each point of the point group, information indicating the direction of a normal extending outside the surface covering the first molecular model at the point,
In the computer,
A process of calculating position information from the additional point in each atomic model in the second molecular model based on the positional information of the additional point and the positional information of each atomic model in the second molecular model. Let it run
The process of calculating the position information of each atomic model in the second molecular model is
When the potential value of the set additional point is positive, the position information of the determined arrangement point, the position information of the additional point stored in the storage unit, and the calculated second molecular model Based on the position information from the additional point in each atomic model, the direction of the normal line at the arrangement point and the direction from the negative charge centroid to the positive charge centroid overlap with the additional point as a center. 5. The position information of each atomic model in the second molecular model is calculated when the position of the additional point is set to the position of the arrangement point when the position is rotated to 5. The calculation support program described in 1. The determining process is as follows:
The calculation support according to any one of claims 1 to 6, wherein a point having the maximum absolute value of the potential at the point is determined as the arrangement point from the point group. program. In the computer,
When the arrangement point is determined, a surface that covers the second molecular model from the group of points, with a normal direction extending inside the surface that covers the first molecular model at the arrangement point as a projection direction To extract the remaining points excluding the points included in the projection figure obtained by projecting onto the surface covering the first molecular model,
Based on the calculated value of the potential at the point, the first molecular model, the second molecular model, and the third molecular model forming the solution model are extracted from the extracted remaining points. Determine placement points to be joined,
The calculation support program according to claim 1, wherein the calculation is executed. The extraction process is:
When the arrangement point is determined, a surface that covers the second molecular model from the group of points, with a normal direction extending inside the surface that covers the first molecular model at the arrangement point as a projection direction To a magnified figure obtained by projecting a projected figure obtained by projecting the first figure onto the surface covering the first molecular model based on the distance from the center point of the projected figure to the outline of the projected figure with the arrangement point as the center 9. The calculation support program according to claim 8, wherein remaining points excluding the included points are extracted. For each point of the point group set on the surface covering the first molecular model arranged on the spatial coordinates, refer to the storage unit that stores the charge value of each atomic model in the first molecular model A potential calculation unit for calculating a value of the potential at the point;
Based on the value of the potential at the point calculated by the potential calculation unit, an arrangement point where the first molecular model and the second molecular model forming the solution model are combined is determined from the point group. A decision unit to
A calculation support apparatus characterized by comprising: Computer
For each point of the point group set on the surface covering the first molecular model arranged on the spatial coordinates, refer to the storage unit that stores the charge value of each atomic model in the first molecular model , Calculate the potential value at the point,
From the point group, based on the value of the potential at the calculated point, determine a placement point where the first molecular model and a second molecular model that forms a solution model are combined.
A calculation support method characterized by executing processing.

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