A virtual screening method for flotation collector molecules for low-rank coal or oxidized coal

Abstract

The present invention discloses a virtual screening method for low-rank coal or oxidized coal flotation collector molecules, comprising the following steps: (1) constructing a coal macromolecular planar model based on detection information, and converting the planar coal model into a 3D minimum energy structure through a molecular force field and molecular dynamics method; (2) subjecting a reagent having the same parent structure to a flotation test; (3) performing a molecular dynamics simulation on the system, and recording the action sites of the reagent molecules on the coal molecules; (4) determining the search range of small molecule conformations during molecular docking; (5) establishing multiple Topomer CoMFA models; (6) obtaining a cross-validation coefficient q2 representing the prediction ability of the model; (7) realizing preliminary screening of collector molecules; and (8) completing virtual screening of collector molecules. The flotation collector molecules suitable for specific low-rank coal or oxidized coal can be screened out from a large drug database in a relatively short time, which will greatly save the research and development cost and production cost of the collector.

Description

Technical Field

[0001] The invention relates to the technical field of collector molecule screening, and in particular to a virtual screening method for low-rank coal or oxidized coal flotation collector molecules. Background Art

[0002] In my country, low-rank coal or oxidized coal resources account for a large proportion. Flotation is one of the most economical and effective methods for coal preparation plants to handle fine-grained coal slime, which can separate useful minerals from gangue minerals based on the difference in hydrophilicity and hydrophobicity of different mineral surfaces. However, the surface of coal particles contains a large number of hydrophilic oxygen-containing functional groups, which makes the coal hydrophilic and not easy to adhere to bubbles and float to become clean coal. Researchers have found that heteropolar flotation agents can improve the flotation effect of low-rank coal or oxidized coal. The use of polar collectors alone will increase the flotation cost. The mixed use of non-polar hydrocarbon oils and polar agents can greatly improve the flotation effect and reduce the cost of coal preparation plants. There are differences in the properties of coal slime in different coal preparation plants, and they have different adaptability to the same collector. The use of empirical exploration to select collectors will increase the research and development cycle of flotation agents. This requires the development model of coal slime flotation collectors to be transformed from traditional empirical trials to precise screening design. Summary of the invention

[0003] In view of the above-mentioned technical deficiencies, the purpose of the present invention is to provide a virtual screening method for flotation collector molecules for low-rank coal or oxidized coal.

[0004] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0005] The present invention provides a method for virtual screening of low-rank coal or oxidized coal flotation collector molecules, comprising the following steps:

[0006] (1) The low-ash clean coal was obtained by the small floating and sinking method for coal structure information detection. The coal macromolecular planar model was constructed based on the detection information. The coal model was corrected using ACD / CNMR predictor software. The planar coal model was converted into a 3D minimum energy structure through molecular force field and molecular dynamics methods.

[0007] (2) conducting flotation tests on reagents with the same parent structure, performing data processing on the flotation results, calculating the combustible recovery rate corresponding to each flotation collector, and using the collector molecule with the highest combustible recovery rate as the template molecule;

[0008] (3) performing molecular force field optimization on the template molecule in step (2) by molecular dynamics method, combining it with the coal molecule in step (1) to construct a reagent-coal interaction system, performing molecular dynamics simulation on the system, and recording the action sites of the reagent molecules on the coal molecules;

[0009] (4) The action site of the reagent in step (3) is used as the active site of the coal, and a cube with a side length of 30 angstroms centered on the active site is used as the active pocket for docking using Autodock software. The active pocket determines the search range of the small molecule conformation during the molecular docking process;

[0010] (5) defining the performance index of the collector molecule in step (2) based on the combustible recovery rate by using Sybyl-X software, cutting the template molecule into fragments according to different standards, and establishing multiple Topomer CoMFA models;

[0011] (6) The Topomer CoMFA model constructed in step (5) was cross-validated using the leave-one-out method to obtain the cross-validation coefficient q representing the model's predictive ability. 2 ;

[0012] (7) Select the one with the highest q 2 The model of the value is converted into a question structure Topomer Search, and the selected database is searched using Topomer Search to achieve a preliminary screening of collector molecules;

[0013] (8) Using the Autodock software, the coal molecule constructed in step (1) is used as the docking receptor, and the active pocket determined in step (4) is used as the ligand active area to carry out molecular docking on the drug molecules screened out in step (7) to obtain the molecular docking energies of different drugs; the collector molecules are sorted according to the molecular docking energy, and the collector molecules with better energy are determined, thereby completing the virtual screening of the collector molecules.

[0014] Preferably, step (2) during the flotation test specifically comprises: adding 80 g of coal into a 1 L flotation tank, adding a collector after slurrying for two minutes, adding a frother after continuing to slurrying for two minutes, and collecting and processing the flotation product after slurrying for 30 seconds.

[0015] Preferably, the molecular dynamics method in step (3) can be replaced by an adsorption model of the reagent-coal molecule, and the stable adsorption position of the reagent on the surface of the coal 3D molecule is used as the active site of the coal macromolecule.

[0016] Preferably, the cross-validation coefficient q is obtained in step (6) 2 When q 2 Models with a value < 0.5 were discarded.

[0017] Preferably, in step (5), at least three cutting methods are used when cutting the template.

[0018] The beneficial effects of the present invention are:

[0019] 1. The virtual screening method of low-rank coal or oxidized coal collector molecules of the present invention can realize the screening of large quantities of similar reagents or even databases, discover collectors with superior performance, and can solve the problems of long cycle and cumbersome process of detecting collector performance through a large number of unit flotation tests.

[0020] 2. The database search method combining quantitative structure-activity relationship and molecular docking adopted in the present invention has the advantages of fast quantitative structure-activity relationship screening and accurate molecular docking screening results, and is more credible than the results of using only one method.

[0021] 3. The present invention constructs a coal model for specific low-rank coal or oxidized coal and completes the screening of the reagent library, taking into account the chemical environment of the functional groups on the surface of actual coal molecules, and can ensure that the screened reagents have good adaptability and pertinence, and have good flotation indicators in industrial practice. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 It is a schematic diagram of the process of the present invention. DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] like Figure 1 As shown, this embodiment provides: a virtual screening method for low-rank coal or oxidized coal flotation collector molecules, comprising the following steps:

[0026] Step 1: Use the small floating and sinking method to obtain low-ash clean coal for coal structure information detection, build a coal macromolecular plane model based on the detection information, use ACD / CNMR predictor software to correct the coal model, and convert the plane coal model into a 3D minimum energy structure through molecular force field and molecular dynamics methods;

[0027] Step 2: Conduct flotation tests on reagents with the same parent structure, process the flotation results, calculate the combustible recovery rate corresponding to each flotation collector, and use the collector molecule with the highest combustible recovery rate as the template molecule;

[0028] The flotation test of this embodiment is as follows: 80g of coal is added to a 1L flotation tank, and a collector is added after slurrying for two minutes, and a frother is added after slurrying for another two minutes, and the flotation product is collected and processed after slurrying for 30 seconds;

[0029] Step 3: Use molecular dynamics software to optimize the molecular force field of the template molecule in step 2, combine it with the coal molecule in step 1 to construct a reagent-coal interaction system, perform molecular dynamics simulation on the system, and record the action sites of the reagent molecules on the coal molecules;

[0030] The molecular dynamics method of this embodiment can be replaced by the adsorption model of the agent-coal molecule, and the stable adsorption position of the agent on the surface of the coal 3D molecule is used as the active site of the coal macromolecule;

[0031] Step 4: The action site of the reagent in step 3 is used as the active site of the coal, and a cube with a side length of 30 angstroms as the center of the active site is used as a docking pocket using Autodock software. The active pocket determines the search range of small molecule conformations during molecular docking; the active space of the coal molecule is determined by the molecular dynamics method, or the oxygen-containing group site on the surface of the coal molecule is directly used as the active space;

[0032] Step 5, using Sybyl-X software to define the performance index of the collector molecule in step 2 with the combustible recovery rate, cutting the template molecule into fragments according to different standards, and establishing multiple Topomer CoMFA models;

[0033] The template molecule is cut in different ways as much as possible to facilitate the selection of the optimal Topomer CoMFA model; in this embodiment, at least three cutting methods are used during cutting;

[0034] Step 6: Use the leave-one-out method to cross-validate the Topomer CoMFA model constructed in step 5 to obtain the cross-validation coefficient q representing the prediction ability of the model. 2 ; In terms of Topomer CoMFA model selection: when the cross-validation coefficient q2>0.5, it indicates that the statistical significance of the model is very obvious, and the model with q2<0.5 is discarded;

[0035] Step 7: Select the one with the highest q 2The model of the value is converted into a question structure Topomer Search, and the selected database is searched using Topomer Search to achieve the preliminary screening of collector molecules; the smaller the energy value of the reagent and the surface active position of the coal molecule docking, the stronger the interaction between the two, and the better the effect of the reagent molecule;

[0036] Step 8: Using the Autodock software, the coal molecule constructed in step 1 is used as the docking receptor, and the active pocket determined in step 4 is used as the ligand active area to perform molecular docking on the drug molecules screened in step 6 to obtain the molecular docking energy of different drugs. The collector molecules are sorted according to the molecular docking energy, and the collector molecules with better energy are determined to complete the virtual screening of the collector molecules.

[0037] This embodiment can screen out flotation collector molecules suitable for specific low-rank coal or oxidized coal from a large drug database in a relatively short time, which has the advantages of short time and high efficiency, and will greatly save the collector R&D cost and production cost.

[0038] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A virtual screening method for low-rank coal or oxidized coal flotation collector molecules, characterized in that: The following steps are involved: (1) The low-ash clean coal was obtained by the small floating and sinking method for coal structure information detection. The coal macromolecular planar model was constructed based on the detection information. The coal model was corrected using ACD / CNMR predictor software. The planar coal model was converted into a 3D minimum energy structure through molecular force field and molecular dynamics methods. (2) conducting flotation tests on reagents with the same parent structure, performing data processing on the flotation results, calculating the combustible recovery rate corresponding to each flotation collector, and using the collector molecule with the highest combustible recovery rate as the template molecule; (3) performing molecular force field optimization on the template molecule in step (2) by molecular dynamics method, combining it with the coal molecule in step (1) to construct a reagent-coal interaction system, performing molecular dynamics simulation on the system, and recording the action sites of the reagent molecules on the coal molecules; (4) The action site of the reagent in step (3) is used as the active site of the coal, and a cube with a side length of 30 angstroms centered on the active site is used as the active pocket for docking using Autodock software. The active pocket determines the search range of the small molecule conformation during the molecular docking process; (5) defining the performance index of the collector molecule in step (2) based on the combustible recovery rate by using Sybyl-X software, cutting the template molecule into fragments according to different standards, and establishing multiple Topomer CoMFA models; (6) The Topomer CoMFA model constructed in step (5) was cross-validated using the leave-one-out method to obtain the cross-validation coefficient q representing the model's predictive ability. 2 ; (7) Select the one with the highest q 2 The model of the value is converted into a question structure Topomer Search, and the selected database is searched using TopomerSearch to achieve a preliminary screening of collector molecules; (8) Using the Autodock software, the coal molecule constructed in step (1) is used as the docking receptor, and the active pocket determined in step (4) is used as the ligand active area to carry out molecular docking on the drug molecules screened out in step (7) to obtain the molecular docking energies of different drugs; the collector molecules are sorted according to the molecular docking energy, and the collector molecules with better energy are determined, thereby completing the virtual screening of the collector molecules.

2. A virtual screening method for low-rank coal or oxidized coal flotation collector molecules according to claim 1, characterized in that: Step (2) during the flotation test specifically includes: adding 80 g of coal into a 1 L flotation tank, adding a collector after slurry mixing for two minutes, adding a frother after continuing to slurry mix for two minutes, and collecting and processing the flotation product after slurry mixing for 30 seconds.

3. A virtual screening method for low-rank coal or oxidized coal flotation collector molecules according to claim 1, characterized in that: The molecular dynamics method in step (3) can be replaced by the adsorption model of the reagent-coal molecule, and the stable adsorption position of the reagent on the surface of the coal 3D molecule is used as the active site of the coal macromolecule.

4. A method for virtual screening of low-rank coal or oxidized coal flotation collector molecules as claimed in claim 1, characterized in that: The cross-validation coefficient q is obtained in step (6) 2 When q 2 Models with a value < 0.5 were discarded.

5. A method for virtual screening of low-rank coal or oxidized coal flotation collector molecules as claimed in claim 1, characterized in that: In step (5), at least three cutting methods are used when cutting the template.

Images