Simulation cycle implementation method, simulation cycle implementation system, program and program storage medium

Abstract

To provide a simulation cycle implementation method, simulation cycle implementation system, program and program storage medium suitable for computer simulation of an object having a wide variety of biochemical reactions such as biological cells and biological tissues.SOLUTION: A simulation cycle implementation system for constructing a model of a biochemical reaction, simulating it, feeding back a result, modifying the model, and repeating the simulation and subsequent processes includes: a structured reaction formula input unit to which a structured reaction formula is input, the structured reaction formula having an expression form in which all of a plurality of nodes are connected to each other by links; and a display unit on which the structured reaction formula input to the structured reaction formula input unit is displayed. The simulation cycle implementation system is characterized in that the simulation is repeated by using the structured reaction formula as a direct input, and the reaction formula can partially include an expression including three or less nodes.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to, for example, a method for implementing a simulation cycle, a system for implementing a simulation cycle, a program, and a program storage medium, and in particular to a method for implementing a simulation cycle, a system for implementing a simulation cycle, a program, and a program storage medium that are suitable for computer simulation of objects having a wide variety of biochemical reactions, such as biological cells and biological tissues. [Background technology]

[0002] In research and development, constructing models of cells or tissues and simulating them on a computer is carried out. In this case, a series of cycles (hereinafter also referred to as "simulation cycles"), including constructing a model by a user, running a computer simulation, interpreting the results of the simulation by the user, modifying the model by the user, and running a computer simulation using the modified model, are repeated many times.

[0003] This repeated simulation cycle is not only performed many times until the model is completed, but even after the model is completed, many more simulation cycles are performed to perform simulations that correspond to drug stimuli given to the cells or tissues, and different states of the cells or tissues (e.g., many different states due to differences in protein concentration, differences in gene expression, differences between species, etc.).

[0004] The model shared between the user and the computer in the above-mentioned simulation cycle is primarily expressed in what are collectively called biochemical reactions.

[0005] Biochemical reaction models are represented as nodes and links between one or more reactants and one or more reaction products, connected by arrows that indicate the direction of reaction progress, and the links represented by the arrows are assigned symbols with rate constants that determine the speed of the reaction, which is used as a global standard method of representation.

[0006] For example, the simplest reaction, in which substance A changes into substance B, is represented by a link with an arrow pointing from node A to node B between reactant A and reaction product B, and a rate constant is assigned to the vicinity of the link. In addition, in a second-order reaction (for example, a reaction in which substances C and D combine to produce substance E), C+D, which represents the bond, is represented as one node, and E, the complex, is represented as another node, with an arrow pointing from C+D to E between them represented as a link, and a rate constant is assigned to the vicinity of the link.

[0007] Biochemical reactions that proceed in cells and tissues involve a variety of substances including proteins, and are more complex than any other example in terms of the number of substance species, with each substance species reacting with a very large number of other substance species. In the above simulation cycle, in order to represent such biochemical reactions as a whole, a biochemical reaction with one link as a unit, or a biochemical reaction with three nodes and two links as a unit, was represented independently, and a simple collection of multiple biochemical reaction equations obtained by representing each of these multiple biochemical reactions independently was used as the overall representation of the model.

[0008] Meanwhile, a method has been reported in which categorized reaction patterns are provided as templates, and biochemical reactions are graphically represented and simulated by combining them (Patent Document 1, Non-Patent Documents 1, 2, 3).

[0009] However, the invention of Patent Document 1 was an invention of a means for achieving both the graphical representation of biochemical reaction equations and computer simulation, and was not an invention that focused on using the graphically represented biochemical reaction equations in the above-mentioned simulation cycle that is repeated multiple times.

[0010] Although Patent Document 3 also refers to relationships between linked biopolymers, it focuses on cases where the linkage has not been obtained by exploring strict biochemical reactions (such as correlations in gene expression), i.e., problems with linked relationships between biopolymers that do not represent strict biochemical reactions, and on methods for obtaining linkage information and displaying it, but does not address issues in using the information during a simulation cycle. [Prior art documents] [Patent documents]

[0011] [Patent Document 1] JP 2002-007380 A [Patent Document 2] JP 2004-129626 A [Patent Document 3] Patent No. 4167417 [Non-patent literature]

[0012] [Non-Patent Document 1] Ichikawa, K., “A-Cell: graphical user interface for the construction of biochemical reaction models”, BioinformaticsVol.17(2001), pp.483-484. [Non-Patent Document 2] Ichikawa, K., “A Modeling Environment withThree-Dimensional Morphology, A-Cell-3D, and Ca2+ Dynamics in aSpine”, Neuroinformatics, Vol.3(2005), pp.49-64. [Non-Patent Document 3] Kazutoshi Ichikawa, "A-Cell: Computer software for constructing virtual nerve cells," Biophysics, 46 (2006), pp. 26-32. Summary of the Invention [Problem to be solved by the invention]

[0013] Naturally, the model determines the results of the simulation. However, it is nearly impossible to mathematically analyze what the results will be, except in very simple cases. When an unexpected result is obtained from a simulation, the intuition of humans with outstanding spatial cognitive functions is fundamentally important in identifying the cause. In other words, a model representation based on cognitive representation theory is necessary, and it is essential that the representation is easy for human intuition to work on. At the same time, this model representation must be directly processed by a computer.

[0014] However, biochemical reactions of proteins in cells are more complicated than any other example in terms of the number of substance species, and one substance species reacts with a very large number of other substance species. In other words, using a model expressed as a set of decomposed biochemical reactions consisting of only one or two links in the above simulation cycle greatly hinders human understanding, making it virtually impossible to understand.

[0015] Therefore, it was impossible to gain intuitive insight into why the simulation results were as they were, or how to achieve the desired results, from a model that was represented as a collection of decomposed biochemical reactions consisting of only one or two links.

[0016] Under the above circumstances, there is a big obstacle to efficiently performing multiple simulation cycles of cells and tissues. The present invention has been made with the intention of solving such problems, and generally, the object of the present invention is to solve the problems in performing multiple simulation cycles. That is, the object of the present invention is to provide a method for performing a simulation cycle, a system for performing a simulation cycle, a program, and a program storage medium that enable a user to intuitively gain insight into the relationship between the simulation results and the model. More specifically, the primary object of the present invention is to provide a method for performing a simulation cycle, a system for performing a simulation cycle, a program, and a program storage medium that enable a model representation that can be easily understood by a user performing the simulation and that allows the user to grasp the overall picture to be shared with a computer when performing a computer simulation of an object having a wide variety of biochemical reactions such as biological cells and biological tissues, and that enables the model representation to be input directly into the computer to repeat the simulation cycle.

[0017] Another object of the present invention is to provide a method for implementing a simulation cycle, a system for implementing a simulation cycle, a program, and a program storage medium that make it possible to make maximum use of human intuition. [Means for solving the problem]

[0018] In order to solve the above problems, the present inventor focused on cognitive representation and continued research and development, resulting in the concept of a system that introduces a structured reaction equation that enables users to intuitively understand the relationship between the simulation results and the model, and performs multiple simulation cycles. A structured reaction equation that can be intuitively understood by users based on cognitive representation is adopted as a model representation, and this model representation is directly input and processed by a computer, thereby quickly and efficiently performing multiple simulation cycles.

[0019] Therefore, in order to solve the above-mentioned problems, a simulation cycle implementation system according to a first aspect of the present application is a simulation cycle implementation system in which a model of a biochemical reaction is constructed, simulated, the results are fed back to change the model, and the simulation and subsequent steps are repeated, in which when a biochemical reaction model expressed by two or more nodes corresponding to reactants and reaction products each containing one or more substances and links representing biochemical reactions between the nodes includes four or more nodes that are directly and / or indirectly related to each other, the whole is not expressed as a set of biochemical reactions with two or three nodes and one or two links as a unit, but rather has an expression format in which all of the multiple nodes are linked to each other without breaking the links between the four or more nodes, which may include indirect reaction relationships that are not in a direct reaction relationship, and a display unit that displays the structured reaction formula inputted to the structured reaction formula input unit, and a simulation is performed by using the structured reaction formula as a direct input, and the simulation is repeated, and the reaction formula can partially include an expression including three or less nodes.

[0020] As a second aspect of the present invention, in the first aspect, at least a model construction / modification unit, a simulation execution unit, and a simulation result display unit may be involved in executing the repetition of the simulation.

[0021] As a third aspect of the present invention, in the second aspect, the model construction / modification unit may be configured to include a model construction means for constructing and displaying a part or the whole of a model of a structured reaction formula by using direct input of a structured reaction formula from a user or data from a biochemical reaction internal / external database and a model internal / external database.

[0022] As a fourth aspect of the present invention, in the second aspect, the simulation execution unit may be configured to include a model conversion means for converting the structured reaction equation model constructed by the model construction / modification unit, a simulation program generation / storage means for generating and storing a simulation program from the converted model, and a simulation program execution means for executing the simulation program.

[0023] As a fifth aspect of the present invention, in the second aspect, the simulation result display unit may be configured to include a simulation result display means for displaying a simulation result.

[0024] As a sixth aspect of the present invention, in the first aspect, each process in which the model construction / modification unit, the simulation execution unit, and the simulation result display unit operate may use a single program or a combination of multiple programs, and may include a user operation receiving unit that receives user operations during the execution of the single or multiple programs.

[0025] As a seventh aspect of the present invention, in the first aspect, one or more semantically related biochemical reaction formulas are represented as blocks, and in a macroscopic model representation in which the blocks are connected by links that represent the relationships between the blocks, the biochemical reaction formulas represented by nodes and links represented as a lower level of each block may include structured reaction formulas.

[0026] As an eighth aspect of the present invention, in the seventh aspect, in a further macroscopic ultra-macroscopic model representation in which the macroscopic model representation is configured in a multiple hierarchical structure, a structured reaction formula may be included in a group including a biochemical reaction formula constituting the lowest layer of the ultra-macroscopic model representation.

[0027] As a ninth aspect of the present invention, in the first aspect, the system may further comprise a differential equation generating unit that generates a differential equation from the structured reaction equation without user intervention.

[0028] As a tenth aspect of the present invention, in the first aspect, the structured reaction formula may include nodes and links based on intermolecular interactions obtained from molecular dynamics calculations.

[0029] As an eleventh aspect of the present invention, in the system in the first aspect using the structured reaction formula as a model representation, the structured reaction formula may be constructed by a user, or may be automatically constructed by software using an unstructured reaction formula or a combination of an unstructured reaction formula and a structured reaction formula.

[0030] As a twelfth aspect of the present invention, in the first aspect, the present invention may be used in at least one of the following: research and development of pharmaceuticals, research and development of cosmetics, food research and development, research and development of treatments, treatment sites, research and development related to beauty, cell and tissue testing work, research and development related to health promotion, research and development related to disease prevention, research and development activities targeting cells and tissues at research and educational institutions including universities, or educational activities associated therewith.

[0031] As a thirteenth aspect of the present invention, in the second aspect, the model construction and correction unit may include a substance name / biochemical reaction formula name input / designation unit, a biochemical reaction formula function group designation unit, and a structured reaction formula automatic generation unit, and the model construction and correction unit may be capable of referring to a biochemical reaction internal / external database and / or a model internal / external database.

[0032] As a fourteenth aspect of the present invention, in the thirteenth aspect, the automatic structured reaction formula generation unit may include a substance name spatial arrangement determination unit within a biochemical reaction formula functional group, a substance link arrangement determination unit within a biochemical reaction formula functional group, a rate constant arrangement determination unit, and an automatic structured reaction formula generation confirmation unit.

[0033] In order to solve the above-mentioned problems, a method for implementing a simulation cycle according to a fifteenth aspect of the present application is a simulation cycle implementation system in which a model of a biochemical reaction is constructed, simulated, the results are fed back to modify the model, and the simulation and subsequent steps are repeated, in which when a biochemical reaction model expressed by two or more nodes corresponding to reactants and reaction products each containing one or more substances and links representing biochemical reactions between the nodes includes four or more nodes that are directly and / or indirectly related to each other, a structured reaction formula having an expression format in which all of the multiple nodes are mutually linked without disconnecting the links between the four or more nodes, which may include an indirect reaction relationship that is not in a direct reaction relationship, is input, the structured reaction formula inputted in the structured reaction formula input unit is displayed on a display unit, and a simulation is performed using the structured reaction formula as a direct input, thereby repeating the simulation, characterized in that the structured reaction formula can partially include an expression including three or less nodes.

[0034] Furthermore, in order to solve the above-mentioned problems, a program according to a sixteenth aspect of the present application is a simulation cycle implementation system in which a model of a biochemical reaction is constructed, simulated, the results are fed back to modify the model, and the simulation and subsequent steps are repeated, the program causing a computer to function as: a structured reaction formula input unit into which a structured reaction formula having an expression format in which all of a plurality of nodes are mutually linked without disconnecting the links between the four or more nodes, which may include an indirect reaction relationship that is not in a direct reaction relationship, is input when a biochemical reaction model expressed by two or more nodes corresponding to reactants and reaction products each containing one or more substances and links representing biochemical reactions between the nodes includes four or more nodes that are directly and / or indirectly related to each other is input; and a display unit for displaying the structured reaction formula input to the structured reaction formula input unit, the program being characterized in that the simulation is repeated by performing a simulation using the structured reaction formula as a direct input, and the structured reaction formula can partially include an expression including three or less nodes.

[0035] Another aspect of the present invention is realized as a storage medium having a program according to the sixteenth aspect of the present application recorded thereon. Effect of the Invention

[0036] According to each aspect of the present invention, when a biochemical substance at a certain node changes, the spatial cognition ability of the observer is directly mobilized to understand the order in which it propagates throughout the entire system, and the relationship between nodes is clearly understood at a glance, so that the user can intuitively grasp the entire complex interactions between substances, and it is possible to incorporate a common expression method that can be directly input to a computer into the simulation cycle, accelerating research and development using simulations and enabling the execution of simulations with complex settings that could not be performed before. Moreover, since human intuition can be utilized to the maximum extent, understanding and ideas are promoted, and it is also possible to prevent misunderstandings. [Brief description of the drawings]

[0037] [Figure 1] FIG. 1 is a conceptual diagram for generally explaining a method for performing a simulation cycle according to one embodiment of the present invention. [Figure 2A] FIG. 1 is a conceptual diagram for explaining a non-structuring reaction formula. [Figure 2B] FIG. 1 is a conceptual diagram for explaining a structuring reaction formula according to the present application. [Diagram 3] 1 is a conceptual block diagram showing the overall configuration of a computer system constituting one embodiment of the present invention. [Figure 4] 1 is a conceptual block diagram showing a configuration of a simulation cycle implementation system according to an embodiment of the present invention. [Diagram 5] FIG. 2 is a functional block diagram of a simulation cycle implementation program in the simulation cycle implementation system according to one embodiment of the present invention. [Figure 6] FIG. 2 is a software block diagram showing a case where a structured reaction formula according to an embodiment of the present application is automatically generated by a computer. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038] In one embodiment of the present invention described below, the starting point is that the above-mentioned problems can be solved by adopting a common representation method that is easy for humans to understand and intuitive, and can also be processed by a computer, that is, a structured biochemical reaction equation (structured reaction equation) as a representation based on cognitive representations, during the simulation cycle.

[0039] Hereinafter, a system / method for performing a simulation using a structured reaction equation according to one embodiment of the present invention will be described in detail with reference to the drawings.

[0040] One embodiment of the present invention relates to the implementation of a simulation cycle shown in FIG. 1. That is, FIG. 1 is a conceptual diagram for generally explaining a method for implementing a simulation cycle according to one aspect of the present invention. In a general, universal simulation of a cell or biological tissue that is not the present invention (not shown), a simulation is performed using an unstructured reaction equation. In contrast, in a simulation of a cell or biological tissue in a method for implementing a simulation cycle according to one aspect of the present invention, as shown in FIG. 1, a structured biochemical reaction equation model (2) is constructed based on literature information or experimental data (1) using, for example, cell simulation software (not shown), and the constructed structured biochemical reaction equation model is displayed on a computer screen (not shown). The displayed model may be one directly input by a user, or may be one that is automatically or semi-automatically displayed based on a specific algorithm by an information processing device (not shown) based on biochemical reaction information obtained from a database or the like. This model is directly input into the simulation software, where it is analyzed and interpreted, and a simulation is performed (3). Meanwhile, the user predicts the results (4). The simulation results are then analyzed, predicted (4), and compared with the literature and experimental data on which the model was built (5). This comparison is fed back to modify the model (2), and the simulation is run again (3). This simulation cycle is repeated many times to arrive at a final conclusion (6).

[0041] In this way, the structured biochemical reaction equation model (2) in Fig. 1 is shared between the human user and the computer, and if this model representation can be intuitively understood by humans, it is expected that a large number of simulation cycles can be repeated efficiently, effectively, and without stress for the user, resulting in a faster simulation cycle. In one embodiment of the present invention, in order to achieve this purpose, a system employing the structured biochemical reaction equation model (2) is constructed as shown in Fig. 1.

[0042] Fig. 2, which is a conceptual diagram for explaining the difference between an unstructured reaction formula (Fig. 2A) and a structured reaction formula (Fig. 2B) according to the present application, shows examples of screens on which the unstructured reaction formula (Fig. 2A) and the structured reaction formula (Fig. 2B) are displayed. Both indicate the same biochemical reaction that gives exactly the same simulation results, but the unstructured reaction formula (Fig. 2A) is expressed as a set of multiple independent biochemical reaction formulas expressed, for example, with two nodes (201 and 202) and one link (203), or three nodes (204, 205, 206) and two links (207, 208).

[0043] In contrast, in the structured reaction equation (Fig. 2B), all nodes are interconnected, and when a biochemical substance at a node changes, it is possible to intuitively grasp at a glance the order in which it propagates throughout the system. In this example, it is also possible to intuitively grasp what the final state will be.

[0044] For example, in an unstructured reaction equation (Figure 2A), if one tries to understand the relationship between node 201 and node 206, one must logically trace the relationships between all nodes from 201 to node 206, which takes time and causes great stress for humans. In contrast, in a structured reaction equation (Figure 2B), the spatial cognition ability of humans is directly mobilized, and the relationship between node 209 and node 210 can be clearly understood at a glance.

[0045] In an embodiment of the present invention, the structured reaction equation representation, which is either directly input by a user or automatically or semi-automatically constructed from a biochemical reaction database, is incorporated into a simulation cycle.

[0046] A conceptual block diagram showing the overall configuration of a computer system constituting one embodiment of the present invention is shown in FIG. 3. Here, only the important components constituting this embodiment are shown, and components normally provided such as a power supply are not shown, but this embodiment may include such normally provided components. That is, as shown in FIG. 3, a computer system 30 according to this embodiment is configured to include a calculation processing / main memory 310, a keyboard / mouse / display (or other input / output devices) 320 connected to the calculation processing / main memory 310, a biochemical reaction external database 330 and a model external database 340 each connected to the calculation processing / main memory 310 via, for example, a communication line TL, and a biochemical reaction internal database 350 and a model internal database 360 ​​each internally connected to the calculation processing / main memory 310. However, in the above embodiment, a case is shown in which four databases, namely, biochemical reaction external database 330-A, model external database 340-A, biochemical reaction internal database 330-B, and model internal database 340-B, are provided. However, in the present invention, it is not necessarily necessary to provide all four databases at the same time, and it is sufficient to have at least one of these four databases.

[0047] The above computer system is used, and a new structured reaction formula is constructed by a user using a keyboard or mouse 320, or a structured reaction formula is constructed by combining or modifying biochemical reaction formulas obtained from the biochemical reaction internal database 330-B in the computer system and the biochemical reaction external database 330-A via the communication line TL, or a biochemical reaction model obtained from the model internal database 340-B and the model external database 340-A via the communication line TL is read and corrected or modified to construct a new structured reaction formula as a model. However, although the above embodiment shows a case in which both the biochemical reaction internal database 330-B and the biochemical reaction external database 330-A are provided at the same time, the present invention may also be configured to include either one of the biochemical reaction internal database 330-B and the biochemical reaction external database 330-A. Similarly, the above embodiment shows a case in which both the model internal database 360 ​​and the model external database 340-A are provided at the same time, the present invention may also be configured to include either one of the model internal database 340-B and the model external database 340-A.

[0048] 4 is a conceptual block diagram showing the configuration of a simulation cycle implementation system according to an embodiment of the present invention using the above computer system. The system 40 is configured to include at least a model construction / modification unit 410, a simulation execution unit 420, a simulation result display unit 430, a biochemical reaction internal / external database 330 and a model internal / external database 340, each connected to the model construction / modification unit 410, and a simulation result database 460 connected (for example, internally) to the simulation execution unit 420 and the simulation result display unit 430. A structured reaction equation model is constructed in the model construction / modification unit 410 while referring to information in the biochemical reaction internal / external database 330 and the model internal / external database 340 as necessary, and is displayed on the display. Modification is also performed in a similar manner.

[0049] The constructed or modified structured reaction equation model is simulated in the simulation execution unit 420. The simulation results are stored in the simulation result database 460.

[0050] When the simulation is completed, the simulation result display unit 430 reads the simulation result from the simulation result database 460 and displays it on the display. After that, the result analysis and examination of Fig. 1 are performed, and the model construction and modification unit 410 modifies the model, and the simulation cycle shown in Fig. 1 is performed multiple times.

[0051] Fig. 5 shows a functional block diagram of a simulation cycle execution program in the simulation cycle execution system according to one embodiment of the present invention shown in Fig. 4. As shown in Fig. 5, the entire program 50 is configured to include a model construction / modification unit 410, a model conversion unit 520, a simulation program generation / storage unit 530, a simulation execution unit 420, a simulation result display unit 430, a biochemical reaction internal / external database 330, a model internal / external database 340, a simulation program database 580, and a simulation result database 460. For example, the biochemical reaction internal / external database 330 is internally connected to the model construction / modification unit 410, the model internal / external database 340 is internally connected to the model construction / modification unit 410 and the model conversion unit 520, the simulation program database 580 is internally connected to the simulation program generation / storage unit 530 and the simulation execution unit 420, and the simulation result database 460 is internally connected to the simulation execution unit 420 and the simulation result display unit 430. However, while the above embodiment shows a case in which both the internal / external biochemical reaction database 330 and the internal / external model database 340 are provided simultaneously, the present invention may also be configured to provide only one of the internal / external biochemical reaction database 330 and the internal / external model database 340.

[0052] In the model construction / modification section 410, a structured reaction equation model is constructed using the internal / external biochemical reaction database 330 and displayed on a display (not shown). At this time, the reaction pattern template described in Patent Document 1 and its additional modification template may be used.

[0053] The constructed structured reaction equation model is subjected to analysis of the model structure by the model conversion unit 520, and converted into a form that can be calculated by a computer, such as a differential equation, and a computer program capable of numerical calculation is generated and stored in the simulation program database 580.

[0054] A simulation program may be written by a user based on the representation that has been converted into a computable form.

[0055] In the simulation execution unit 420, the simulation program stored in the simulation program database 580 is compiled to generate an executable program, and the simulation is started. The simulation results are stored in the simulation result database 460.

[0056] The data stored in the simulation result database 460 is read into the simulation result display unit 430 and, if necessary, is displayed on a display (not shown) as a number string, a 2D graph, a 3D graph, a 3D spatial distribution, or the like.

[0057] Based on the displayed simulation results, the user can analyze and examine the simulation results.

[0058] Even in the model representation of a structured reaction formula, when the model becomes complicated, the model is represented by many nodes and links, so that it is difficult for humans to grasp the overall structure. In this case, in the present application, for example, a plurality of biochemical reaction formulas may be grouped by function or by reaction type to form a block containing a plurality of biochemical reaction formulas, and the relationship between these plurality of blocks may be represented by links. Furthermore, a plurality of blocks may be integrated and represented as a higher-level functional block, resulting in a hierarchical structure of the blocks. Even in these cases, the lowest layer of the block is a biochemical reaction formula, and in the embodiment of the present invention, the lowest layer of the block is model-represented by a structured reaction formula.

[0059] A system using a structured reaction equation according to one embodiment of the present invention as a model expression can be used in any activity targeting cells or tissues, including, but not limited to, pharmaceutical research and development, cosmetics research and development, food research and development, treatment research and development, treatment sites, beauty research and development, cell and tissue testing work, health promotion research and development, disease prevention research and development, and university and other research and education.

[0060] In the above embodiment, a structured reaction formula is provided by a human being and the simulation is started, but the present invention may be such that the structured reaction formula is automatically provided by the system based on an algorithm, for example. This will be described below.

[0061] In the functional block diagram of a simulation cycle execution program in a simulation cycle execution system according to another embodiment of the present invention, a program configuration diagram in the case where a structured reaction equation is automatically constructed by the program is shown in Fig. 6. This program configuration diagram can also be considered as a detailed illustration of the internal structure of the model construction / modification unit 410 in Fig. 5 in the automatic construction.

[0062] That is, in this embodiment, for example, the model construction / modification unit 410 is configured to include a substance name / biochemical reaction formula name input / designation unit 4110, a biochemical reaction formula functional group designation unit 4120, and a structured reaction formula automatic generation unit 4130, and is externally provided with a biochemical reaction internal / external database 4140 and a model internal / external database 4150 that the model construction / modification unit 410 may refer to as appropriate. The structured reaction formula automatic generation unit 4130 further includes a "substance name spatial arrangement determination unit within biochemical reaction formula functional group" 4132, a "substance link arrangement determination unit within biochemical reaction formula functional group" 4134, a rate constant arrangement determination unit 4136, and an automatic structured reaction formula generation confirmation unit 4138. However, although the above shows a case in which both the biochemical reaction internal / external database 330 and the model internal / external database 340 are simultaneously provided, it is not necessarily necessary to provide both simultaneously, and at least one of them may be provided.

[0063] When a structured reaction formula is automatically constructed by a program, the substance names included in the structured reaction formula are input and specified in a substance name / biochemical reaction formula name input / specification section 4110 (a flow chart is not shown; the same applies below). Next, which substance / biochemical reaction formulas are to be grouped into one functional group is specified in a biochemical reaction formula functional group specification section 4120. This specification may be made by inputting the substance name or biochemical reaction formula name from a keyboard or the like, or by specifying a list.

[0064] The spatial arrangement of substance names is determined in the "substance name spatial arrangement determination unit within biochemical reaction formula functional group" 4132 constituting the structured reaction formula automatic generation unit 4130 that automatically generates structured reaction formulas based on the input / specified substance name, biochemical reaction formula name, and information on the biochemical reaction formula functional group, and based on information on the biochemical reaction internal / external database 330 and / or the model internal / external database 340. At this time, the spatial arrangement is determined taking into consideration the number of characters in the substance names and the links between substances.

[0065] Next, the connection structure of the links between substances is determined in the "substance link arrangement determination unit within biochemical reaction formula functional group" 4134 constituting the structured reaction formula automatic generation unit 4130, and then the arrangement of the rate constants associated with each link is determined in the rate constant arrangement determination unit 4136.

[0066] Finally, the automatically generated structured reaction formula is displayed on the display and confirmed by the user in the automatic structured reaction formula generation confirmation unit 4138. Here, the automatically generated structured reaction formula may be corrected by the user.

[0067] In each of the above steps, the biochemical reaction internal / external database 330 and / or the model internal / external database 340 are / is referred to as necessary. [Industrial Applicability]

[0068] According to each aspect and embodiment of the present invention, when using cell and tissue simulation for research and development of cells, tissues, and living organisms, including drugs, cosmetics, and food, or for education and research at universities, etc., introducing structured reaction equations into the simulation cycle makes the most of the user's intuition, quickly finding corrections and identifying causes, and as a result, speeding up research and development, reducing costs, enriching content, and promoting and deepening understanding. Therefore, the present invention has great applicability in various industries, including pharmaceuticals, cosmetics, foods, medicine, beauty, etc. [Explanation of symbols]

[0069] 30 Computer Systems 40 Simulation cycle implementation system 50 Simulation Cycle Implementation Program 310 Processing and main memory 320 Keyboard, mouse, display (and other input / output devices) 330 Biochemical Reaction Internal and External Database 330-A Biochemical Reaction External Database 330-B Biochemical Reaction Internal Database 340 Model Internal and External Databases 340-A Model External Database 340-B Model Internal Database 410 Model Construction and Modification Department 4110 Substance name / biochemical reaction formula name input / designation section 4120 Biochemical reaction formula functional group designation part 4130 Automatic Structured Reaction Equation Generation Unit 4132 Biochemical reaction function group substance name spatial arrangement determination part 4134 Substance link arrangement determination part in biochemical reaction function group 4136 Rate constant arrangement determination part 4138 Automatic Structured Reaction Formula Generation and Verification Unit 420 Simulation Execution Department 430 Simulation result display section 460 Simulation Results Database 520 Model Conversion Unit 530 Simulation program generation and storage unit 580 Simulation Program Database

Claims

1. In a simulation cycle implementation system in which a model of a biochemical reaction is constructed, simulated, the results are fed back to change the model, and the simulation and subsequent steps are repeated, a structured reaction formula input unit for inputting a structured reaction formula having an expression format in which a plurality of nodes are mutually linked as a whole without disconnecting the links between the four or more nodes, which may include an indirect reaction relationship that is not a direct reaction relationship, rather than being expressed as a set of biochemical reactions with two or three nodes and one or two links as a unit, when a biochemical reaction model expressed by two or more nodes corresponding to reactants and reaction products each containing one or more substances and links representing biochemical reactions between the nodes includes four or more nodes that are directly and / or indirectly related to each other; a display unit on which the structured reaction formula inputted in the structured reaction formula input unit is displayed; having A simulation cycle execution system, characterized in that a simulation is repeated by performing a simulation using the structured reaction equation as a direct input, and the structured reaction equation can partially include an expression including three or less nodes.

2. 2. The simulation cycle execution system according to claim 1, wherein at least a model construction / modification section, a simulation execution section, and a simulation result display section are involved in the execution of said repeated simulations.

3. 3. The simulation cycle implementation system according to claim 2, wherein the model construction / modification unit is provided with a model construction means for constructing and displaying a part or the whole of a model of a structured reaction formula by using direct input of a structured reaction formula from a user or data from a database including at least one of a biochemical reaction external database, a model external database, a biochemical reaction internal database, and a model internal database.

4. 3. The simulation cycle implementation system according to claim 2, wherein the simulation execution unit comprises: a model conversion means for converting the structured reaction equation model constructed by the model construction / modification unit; a simulation program generation / storage means for generating and storing a simulation program from the converted model; and a simulation program execution means for executing the simulation program.

5. 3. The simulation cycle execution system according to claim 2, wherein said simulation result display section comprises a simulation result display means for displaying the simulation result.

6. 2. The simulation cycle implementation system according to claim 1, wherein each process in which the model construction / modification unit, the simulation execution unit, and the simulation result display unit operate uses a single program or a combination of multiple programs, and further includes a user operation receiving unit that receives user operations during the execution of the single or multiple programs.

7. 2. The simulation cycle implementation system according to claim 1, wherein one or more semantically related biochemical reaction formulas are represented as blocks, and in a macroscopic model representation in which the blocks are connected by links that represent the relationships between the blocks, the biochemical reaction formulas represented by nodes and links that are represented as a lower level of each block include structured reaction formulas.

8. 8. The simulation cycle implementation system according to claim 7, characterized in that in an even more macroscopic ultra-macroscopic model representation in which the macroscopic model representation is constituted in a plurality of hierarchical layers, a structured reaction equation is included in a group including a biochemical reaction equation constituting the lowest layer of the ultra-macroscopic model representation.

9. 2. The simulation cycle implementation system according to claim 1, further comprising a differential equation generating unit for generating a differential equation from the structured reaction equation without user intervention.

10. 2. The system for implementing a simulation cycle according to claim 1, wherein the structured reaction equation can include nodes and links based on intermolecular interactions obtained from molecular dynamics calculations.

11. 2. The simulation cycle implementation system according to claim 1, wherein the structured reaction equation is constructed by a user or is automatically constructed by software from an unstructured reaction equation or a combination of an unstructured reaction equation and a structured reaction equation.

12. The simulation cycle implementation system as described in claim 1, characterized in that it is used in at least one of the following: research and development of pharmaceuticals, research and development of cosmetics, research and development of food, research and development of treatment methods, treatment sites, research and development related to beauty, cell and tissue testing work, research and development related to health promotion, research and development related to disease prevention, research and development activities targeting cells and tissues at research and educational institutions including universities, or activities including educational activities associated therewith.

13. The model construction and correction unit The system includes a substance name / biochemical reaction formula name input / designation unit, a biochemical reaction formula function group designation unit, and a structured reaction formula automatic generation unit, 3. The simulation cycle implementation system according to claim 2, wherein the model construction and correction unit is capable of referring to an internal and external database of biochemical reactions and / or an internal and external database of models.

14. The structured reaction equation automatic generation unit is The simulation cycle implementation system according to claim 13, further comprising: a substance name space arrangement determination unit within a biochemical reaction formula functional group; a substance link arrangement determination unit within a biochemical reaction formula functional group; a rate constant arrangement determination unit; and an automatic structured reaction formula generation confirmation unit.

15. In a simulation cycle implementation system in which a model of a biochemical reaction is constructed, simulated, the results are fed back to change the model, and the simulation and subsequent steps are repeated, When a biochemical reaction model expressed by two or more nodes corresponding to reactants and reaction products each containing one or more substances and links representing biochemical reactions between the nodes includes four or more nodes that are directly and / or indirectly related to each other, a structured reaction equation is input in which the links between the four or more nodes, which may include indirect reaction relationships that are not in a direct reaction relationship, are not expressed as a whole as a set of biochemical reactions with two or three nodes and one or two links, but rather have an expression format in which the multiple nodes are all mutually linked without breaking the links between them, The structured reaction formula inputted in the structured reaction formula input section is displayed on the display section, The simulation is repeated by performing a simulation using the structured reaction formula as a direct input.

1. A method for performing a simulation cycle, comprising the steps of: A method for implementing a simulation cycle, characterized in that the structured reaction equation can partially include an expression including three or less nodes.

16. In a simulation cycle implementation system in which a model of a biochemical reaction is constructed, simulated, the results are fed back to change the model, and the simulation and subsequent steps are repeated, Computer, a structured reaction formula input unit for inputting a structured reaction formula having an expression format in which a plurality of nodes are mutually linked as a whole without disconnecting the links between the four or more nodes, which may include an indirect reaction relationship that is not a direct reaction relationship, rather than being expressed as a set of biochemical reactions with two or three nodes and one or two links as a unit, when a biochemical reaction model expressed by two or more nodes corresponding to reactants and reaction products each containing one or more substances and links representing biochemical reactions between the nodes includes four or more nodes that are directly and / or indirectly related to each other; a display unit on which the structured reaction formula inputted in the structured reaction formula input unit is displayed; A program that functions as A program, characterized in that a simulation is repeated by performing a simulation using the structured reaction formula as a direct input, and the structured reaction formula can partially include an expression including three or less nodes.

17. A storage medium storing the program according to claim 16.

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