KR101375672B1 - Method for Predicting a Property of Compound and System for Predicting a Property of Compound - Google Patents

Abstract

The present invention relates to a method for predicting the properties of a compound and a system for predicting the properties of a compound. More specifically, various properties obtained by using a program and a property information prediction module for quantum mechanical calculation based on an optimal molecular structure. How to manage the data and service according to the user's needs, and the server that calculates and manages the property data and the client that inputs the search condition of the compound and receives the results from the server and displays the results on the screen to predict the properties of the compound It's about the system.
The present invention provides a search function based on molecular names, molecular formulas, and molecular structures through a GUI for user convenience, and is not a simple comparison of numbers of atoms, molecules, and functional groups. Subgraph Isomorphism can be used to directly confirm the structural identity of molecules online.
Therefore, the present invention not only reduces the cost and time required for the experiment, but also makes it possible to estimate the value even when the experiment is impossible, thereby facilitating the R & D activities of related industries, as well as the academic and related fields. Providing reasonable information wherever you need the value will have the effect of making the activity smoother.

Description

Method for Predicting a Property of Compound and System for Predicting a Property of Compound

The present invention relates to a method for predicting the properties of a compound and a system for predicting the properties of a compound. More specifically, various properties obtained by using a program and a property information prediction module for quantum mechanical calculation based on an optimal molecular structure. How to manage the data and service according to the user's needs, and the server that calculates and manages the property data and the client that inputs the search condition of the compound and receives the results from the server and displays the results on the screen to predict the properties of the compound It is about the system.

To date, a method or system for providing chemical and physical properties of compounds has been entered into a database of experimental values and searched textually for these compounds. These databases provide known physical property data for up to 20,000 compounds, and physical properties for other compounds are obtained through experiments as necessary.

Physical and chemical property information of the compound should be measured under the proper design of the experimental instruments and under the controlled experimental conditions to obtain accurate results. Although experimental values can be measured in a laboratory or institution where professional experimental instruments are designed, practitioners who conduct research related to chemical processes require considerable equipment, manpower, cost, and time to obtain all of the properties of a compound. Although property information is needed right now, property data of tens of millions of compounds that do not exist in the existing database cannot be obtained online in real time. Therefore, the conventional method or system has a problem that it is time-consuming and inefficient because it requires a lot of effort and time because it has to be obtained by experiments to obtain the physical property value for a single compound, and therefore, for a large number of compounds for which no experimental value exists. There is an increasing need for a method or system that can provide physical properties to a user in real time.

In addition, the existing search using a database has a lot of difficulties in searching for a compound having a complex molecular structure to search by entering a text.

Therefore, the present inventors have made diligent efforts to solve the above problems, and unlike the prior art disclosed in Korean Patent Publication No. 10-2010-0042453, the program and the property information prediction for quantum mechanical calculation based on the optimal molecular structure It is a server that manages various property data obtained by using the module and service it according to user's needs, and a server that calculates and manages property data and a user who inputs the search condition of a compound and receives the results from the server and displays them on the screen. The system which predicts the physical property of the formed compound was confirmed, and the present invention was completed.

The object of the present invention is to overcome the limitations of the above-mentioned conventional methods and systems and to achieve more reliable and better predictive performance, hydrogen (H), carbon (C), nitrogen (N), oxygen (O), sulfur ( S) A method and system for estimating the properties of pure organic compounds composed of up to 5 elements, including molecules of 25 or less atoms except hydrogen, and the properties of compounds without experimental data In addition to calculating and storing the data in a database, a user may conveniently search for a compound, and at the same time, provide a predictive property of the compound in a user-friendly manner.

In order to achieve the above object, the present invention provides a physical property of a compound by a multiple linear regression-artificial neural network hybrid model, which is an example of a quantitative structure-property relationship (QSPR) model that considers various molecular presenters based on more experimental data. Database consisting of a web application server, a relational database, a file storage, a calculation program for calculating temperature dependency information, and a molecular structure-based search program. Corresponding physical properties are provided to clients according to molecular name, molecular structure, desired temperature range, user search condition, number of elements, molecular weight, InChI (The IUPAC International Chemical Identifier), and physical properties.

In the present invention, the 'compound' is composed of five elements such as hydrogen (H), carbon (C), nitrogen (N), oxygen (O), sulfur (S), and the number of atoms except hydrogen It refers to a pure compound consisting of 25 or fewer molecules, and the reason for limiting the range of compounds to which the predictive model can be applied is mainly due to the fact that among the molecular descriptors used, quantum mechanical calculations are required. If present, it is due to the fact that for the compounds beyond the stated range with the current state of the art, problems arise in terms of accuracy and calculation time. However, even within the above limitations, since there are a great many compounds and industrially important compounds are included, it is considered that the present invention can greatly benefit human society.

Humans today depend on a wide variety of organic compounds, including plastics, fibers, rubber, paints, fertilizers, medicines and fuels, and this trend is expected to intensify. According to the American Chemical Society (ACS), as of July 2010, the total number of compounds registered was over 54,000,000. In comparison, even if the physical property value is only one, the number of experimentally known compounds is only tens of thousands. The physical property value of compounds is essential for the better life of mankind, such as the development of new materials and new drugs, the optimal design of chemical plants, the improvement of the productivity of existing facilities, the development and saving of resources, the securing of safety, and the protection of the environment.

The present invention provides a search function based on molecular names, molecular formulas, and molecular structures through a GUI for user convenience, and is not a simple comparison of numbers of atoms, molecules, and functional groups. Subgraph Isomorphism can be used to directly confirm the structural identity of molecules online.

Therefore, the present invention not only reduces the cost and time required for the experiment, but also makes it possible to estimate the value even when the experiment is impossible, thereby facilitating the R & D activities of related industries, as well as the academic and related fields. Providing reasonable information wherever you need the value will have the effect of making the activity smoother.

1 is a flowchart of a method or system for predicting physical properties of a compound provided by the present invention.
2 is a block diagram of a server / client system of the present invention.
Figure 3 is an example of entering the molecular formula in the search box of the system for predicting the physical properties of the compound.
4 is a search result of a compound including a molecular formula input to a system for predicting the physical properties of the compound.
5 illustrates an example of inputting a molecular structure in a search window of a system for predicting the properties of a compound.
6 is a search result of a compound including a molecular structure input to the system for predicting the physical properties of the compound.
7 is an example of inputting the number of atoms, molecular weight, and the range of physical properties in a search window of a system for predicting the physical properties of a compound.
8 is a result of physical properties of specific compounds with respect to conditions entered into a system for predicting physical properties of compounds.
9 is a result of molecular descriptor values of specific compounds for conditions entered into a system for predicting the properties of the compounds.
FIG. 10 shows the results of quantum mechanical calculations for specific compounds with respect to conditions entered into a system for predicting the properties of the compounds. FIG.
FIG. 11 shows the results of pharmaceutical properties of certain compounds with respect to conditions entered into a system for predicting the properties of the compounds. FIG.
12 is a result of physical properties of certain compounds against temperature range conditions entered into a system for predicting physical properties of the compounds.
FIG. 13 is a result of three-dimensional measurement information of a specific compound with respect to conditions entered into a system for predicting the physical properties of the compound. FIG.
14 is a three-dimensional molecular vibration result of a specific compound for the conditions entered into the system for predicting the physical properties of the compound.
15 is a three-dimensional orbital result of a specific compound against the conditions entered into the system for predicting the properties of the compound.

1 is a flow chart of a method and system for predicting the properties of a compound according to the invention in a consistent manner, the first step of a user logging in to a client capable of accessing a server; A second step of selecting and inputting at least one of a molecular formula, a molecular name, and a molecular structure of a compound to be searched for; A third step of selecting a desired temperature range with respect to physical properties when the second step depends on the temperature of the compound; A fourth step of transmitting, by the client, the information input in the second and third steps to the server; The physical property of the compound input through the information transmitted in the fourth step is received from the molecular information database, file storage having the physical property information, temperature dependency calculation module, molecular structure-based search module and returned to the client from the server The fifth step; A sixth step of returning IR, VCD, and NMR spectra information on the compound input in the second and third steps from the server to the client; A seventh step of returning three-dimensional structure information of the compound input in the second and third steps from the server to the client; And an eighth step of displaying, on the screen, the physical properties, the spectra information, and the 3D structure information transmitted to the client in the fifth to seventh steps. When the compound is selected in the second step, any one or more selected from the number of elements, molecular weight, InChI (The IUPAC International Chemical Identifier), and physical properties may be selected. In the second step, the molecular structure may be selected from a table in which the user has a molecular structure or directly input by the user, and the molecular structure to be input is a whole structure or a part of the whole structure of the molecular structure. In the seventh step, the 3D structure information includes the distance between atoms in the compound molecule, the angle between adjacent atoms, the degree of twisting of the molecule, the molecular frequency, and the orbital.

In another aspect, Figure 2 is a block diagram of a system for predicting the physical properties of the compound of the present invention, the system for predicting the physical properties of the compound is one or more of the molecular formula, molecular name, molecular structure of the compound to be searched by the user In the extended refinement, one or more selected from the number of elements, molecular weight, InChI (The IUPAC International Chemical Identifier), and the property range can be entered. A client displaying VCD, NMR spectra information, and 3D structure information on a screen; A server for calculating and retrieving physical properties, IR, VCD, NMR spectra information, and three-dimensional structure information of a compound input from the client; The server relates to a system for predicting properties of a compound including a web application server, a relational database, a file storage having property information, a calculation module for calculating temperature dependent property information, and a molecular structure-based search module. The molecular structure to be inputted at may be selected from a table having a molecular structure by the user or directly input by the user, and the molecular structure to be inputted is a whole structure or a part of the whole structure of the molecular structure. The 3D structural information transmitted from the server to the client includes a distance between atoms in a compound molecule, an angle between adjacent atoms, a degree of twist of a molecule, a molecular frequency, and an orbital.

The present invention is designed to utilize a variety of physical and chemical properties information starting from a very small information of the molecular formula of the compound. The present invention is designed to utilize a variety of physical and chemical properties information starting from a very small information of the molecular formula of the compound. Physical properties referred to in the present invention include a constant value physical property having one value for a compound and a temperature dependent property having a different value depending on temperature. The constant physical properties referred to in the present invention are molecular weight, normal boiling point, critical temperature, critical pressure, critical volume, critical compression factor, eccentric factor, radius of rotation, absolute entropy of ideal gas, energy generated by ideal gas, production gas of ideal gas Energy, liquid molar volume, heat of fusion, refractive index, water solubility, absolute entropy in standard state, generated energy in standard state, generated Gibbs energy in standard state, heat of combustion in standard state, van der Waals area, van der Waals volume, magnetic susceptibility, Polarization degree, ionization energy, electron affinity, paracode, flash point, lower flash point temperature, lower flash volume percentage, upper flash point temperature, upper flash volume percentage, liquid density at normal boiling point, heat of vaporization at 298.15K, heat of vaporization at normal boiling point The temperature-dependent physical properties referred to in the present invention include at least the heat capacity of the ideal gas, the heat capacity of the liquid, the heat of vaporization, the saturated liquid density, the surface tension, and the liquid thermal conductivity. , Gas thermal conductivity, liquid vapor pressure, fluid viscosity, gas viscosity, and the second virial coefficient.

The property information system of the compound of the present invention is configured in a server / client format. The server consists of a web application server, a relational database containing molecular information, a file storage containing physical property information, a calculation program for calculating temperature dependent property information, and a molecular structure based retrieval program. The client, which is a program used by the actual user to search for property information, implements a predefined network protocol so that the server can search for desired molecules and search for property information about the molecules.

A relational database includes a table containing information necessary for the search of molecules and a table containing information on physical properties. A table containing information necessary for searching for molecules is referred to as a 'mole' table. This table contains the structure of the molecule and the table contains the functional group information of the molecule. Molecular information includes the compound's molecular formula, molecular name, simplified molecular input line entry specification (SMILES), molecular weight, InChIkey (an abbreviated string with a fixed length of 25 characters by applying a hash algorithm to a long InChI string), and radicals. It is used as a calculation factor when searching for property information or calculating a property depending on temperature.

File storage system with property information contains information returned to client according to user's request, property file with constant value, calculation factor file depending on temperature, drug property file, presenter property file It includes a quantum mechanical information file, a molecular thumbnail file, and these files are divided and stored in a folder created using a hessian function for load balancing of the system. The quantum mechanics information file is a file that stores the properties of the orbitals of molecules and the properties of quantum calculations. It is a result file obtained through quantum mechanical calculations and contains information for use as a starting point for secondary additional calculations. It contains information related to the orbitals so that the probability of discovery of the former can be seen in a graphical environment.

The calculation program for calculating the temperature dependent property information checks the properties and executes a calculation module for the corresponding properties to check the molecular coefficients in the module for each property to perform the calculation.

Information on the properties of compound molecules stored on the server is based on quantitative structure-property relationship (QSPR) based on quantum mechanical calculations, unlike physical data based on existing experimental values [Todeschini R., V. Consonni V., Molecular Descriptors for Chemoinformatics : Second , Revised and Enlarged Edition : Volume I / II , Wiley-VCH, 2009] A large number of property information are directly stored by the multiple linear regression-artificial neural network hybrid model. In order to calculate the electronic structure of a molecule by quantum mechanical calculation, the Schrodinger equation is solved by a general theory method to solve the electron energy. In the case of a system with many electrons, the electron correlation is ignored. Hartree-Fock (HF) method using approximation [CCJ Roothan, Rev. Mod. Phys. 23, 69 (1951)]. This approximation introduces a fundamental error in the calculated results and adds a multidimensional theoretical perturbation term to the Post Hartree-Fock method [C. Moller and MS Plesset, Phys. Rev. 46, 618 (1934)], to obtain a more accurate solution, but require a relatively large amount of computation.

In addition, a Gaussian method that combines another method, Hartley-Fork and Post Hartley-Fork [L. A. Curtiss, K. Raghavachari, G. W. Trucks, and J. A. Pople, J. Chem. Phys. 94, 7221 (1991); L. A. Curtiss, K. Raghavachari, P. C. Redfern, V. Rassolov, and J. A. Pople, J. Chem. Phys. 109, 7764 (1998) show very little error in energy prediction, but more computation is required because of the energy calculations for several post-Hartley-Fork methods.

In the present invention, in order to consider the correlation between electrons for molecules consisting of a large number of electrons, density function theory that calculates the ground state using the function of the total energy using the electron density function instead of the wave function to which the multidimensional perturbation term is added ( density functional theory) [R. Seeger and JA Pople, J. Chem. Phys. 66, 3045 (1977)] were used to optimize the molecular structure and calculate the frequency.

In addition, in order to process tens of millions of property information data beyond tens of thousands of molecules, which are processed in the existing experimental value-based database, the molecular search includes all data in a two-dimensional table so that the user responds as quickly as possible without inconvenience. A relational database is expressed using the file system, and a file system that forms a tree structure is used for querying the properties of molecules.

In the server structure, the web application server is exposed to the outside for client access. The web application uses server resources to process functions such as user login, molecular search, and property lookup inside the server system, and then return the results to the client.

After the user logs in, a general search is performed using a molecular formula, a molecular name, and a molecular structure. As shown in FIG. 3, when the molecular formula C6H6 is input, a compound including benzene, which is a compound including C6H6, is shown in FIG. 4. 6 molecules are searched, but if only benzene is entered as the molecular name, when entering C6H6, 5 molecules are not searched and only benzene is searched and displayed on the screen.

In addition, the general search of the present invention includes a search function using a molecular structure, which is a unique function of the physical property information system of the present invention, which is not provided in a conventional experimental value database. You can import a mole file, which is a file that contains various molecular structures, and select the molecular structure in the mole file to use as a search condition, or you can draw the desired molecular structure and perform a search based on the molecular structure. In addition to setting the molecular structure selected in the mole file or the structure entered directly by the user as a condition of the entire structure search, it is part of one of the whole structures, that is, the condition that the selected structure is included in the whole structure. Structure search is possible. Accordingly, if the benzene molecular structure is used as the search condition, the search results can be seen in FIGS. 5 and 6, respectively. FIG. 5 shows only benzene as a result of the overall structure search in the case where benzene is set as the search structure to be searched. FIG. 6 is a search for molecules including a benzene structure in the entire structure. 10055 compounds were searched.

Searches for compounds are also searched by extended search. General search is searched by molecular name, molecular formula, molecular structure, but extended search can be searched by using the number of elements, molecular weight, InChI (The IUPAC International Chemical Identifier) or a range of physical properties. As shown in FIG. 7, the number of basic elements C, H, O, N, and S may be set to a number desired by the user, and the molecular weight may be limited by the user. After inputting the above search conditions in the extended search window shown in FIG. 7 and selecting a compound from the searched compound result list by clicking on the compound, the properties, molecular expression values and quantum mechanics of the compound molecule are shown in FIGS. 8 to 11. The calculated values and the constraint properties are returned to the user's screen and displayed.

In the case of physical properties depending on temperature among physical properties, the desired physical temperature can be directly selected to inquire the physical properties. When the user inputs the desired temperature range, the client sends the temperatures to the server, and the server calculates the temperature-dependent properties by the module for calculating temperature-dependent property information for the temperature, and then returns the value to the client. In the conventional experimental value property database, the experiment has already been performed and can only query the values stored in the database. However, the property information system of the present invention can calculate and inquire a value for a desired temperature range in real time. Figure 12 shows the heat capacity of the ideal gas when the temperature range is set from 273K to 1500K, and shows the two values together to compare the calculated value of the present invention with the value obtained by the experiment for the presence of the experimental value And it can be seen that the heat capacity value of the ideal gas can be obtained by calculation.

In addition, the spectra information of IR, VCD, and NMR are also provided to the client for the compound selected by the user, and as shown in FIGS. 13 to 15, measurement information, molecular frequency, and orbital of the selected compound are also provided. . The measurement information includes the distance between atoms in a compound molecule, the angle of arrangement between atoms, and the like. The molecular vibration represents the direction and intensity of the corresponding molecular vibration in the form of an arrow as shown in FIG. The animation is implemented to move in line with the user, allowing the user to see the image of dynamic molecules. Fig. 15 is orbital information, and the present invention is a result obtained by quantum mechanical calculation, which is unique molecular information that can be provided only in the present invention which cannot be provided in a conventional database.

This chemical information system is not a database that contains only numerical information but is designed to find almost all information about one molecule in one program. Using the defined network protocols in this system, clients can be implemented on both regular PCs and mobile devices.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereto will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (9)

In the method of predicting the physical properties of the compound,
A first step of the user logging in to a client that can access the server;
A second method for selecting and inputting one or more of a molecular formula, molecular name, molecular structure, number of elements C, H, O, N, and S, molecular weight, InChI (The IUPAC International Chemical Identifier), and a property range step;
A third step of selecting a desired temperature range with respect to physical properties when the second step depends on the temperature of the compound;
A fourth step of transmitting, by the client, the information input in the second and third steps to the server;
A molecular information database having physical property prediction values of the compound obtained by the multiple linear regression-artificial neural network hybrid model, and the file storage having the physical property information. A fifth step of receiving a temperature dependency calculation module for calculating physical properties of the temperature range selected in step 3 and a molecular structure-based search module and returning them from the server to the client;
A sixth step of returning IR, VCD, and NMR spectra information on the compound input in the second and third steps from the server to the client;
A seventh step of returning three-dimensional structure information of the compound input in the second and third steps from the server to the client; And 3D structural information including the physical properties, spectra information, distances between atoms in compound molecules, angles between adjacent atoms, degree of torsion of molecules, molecular frequency, and orbitals transmitted to the client in steps 5-7. The eighth step of displaying on the screen; Method of predicting the physical properties of the compound comprising.
delete The method of claim 1, wherein in the second step, the molecular structure is selected from a table having a molecular structure by a user or directly input by a user, and the input molecular structure is selected from among the entire structure or the entire structure of the molecular structure. A method of predicting the physical properties of a compound, characterized in that a portion is input.
delete A computer-readable storage medium having recorded thereon a program for executing on a computer a method for predicting the physical properties of a compound according to claim 1.
In the system for predicting the physical properties of the compound,
Select and enter one or more of the molecular formula, molecular name, molecular structure, number of elements C, H, O, N, S, molecular weight, InChI (The IUPAC International Chemical Identifier), and physical property range of the compound 3D structural information including properties returned from accessible server, IR, VCD, NMR spectra information, distance between atoms in compound molecule, angle between adjacent atoms, degree of torsion of molecules, molecular frequency, orbital Client;
A server for calculating and retrieving physical properties, IR, VCD, NMR spectra information, and 3D structure information of the compound input from the client; And
The server is a web application server, a relational database including a table containing information necessary for the retrieval of molecules and a table containing information on physical properties, predicted properties of compounds obtained by a multiple linear regression-artificial neural network hybrid model, and temperature dependence. Predict physical properties of compounds, including physical properties calculation factors, pharmaceutical properties, molecular descriptors, pile storage containing quantum mechanical information, calculation modules for calculating temperature dependent property information for selected temperature ranges System.
delete The molecular structure of claim 6, wherein the molecular structure input from the client is selected from a table having a molecular structure by a user or directly input by the user, and the input molecular structure is the entire structure or the entire structure of the molecular structure. A system for predicting the physical properties of a compound, characterized in that a part of the input.



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