CN103049677A - Computing method for processing interaction between small molecules and proteins - Google Patents
Computing method for processing interaction between small molecules and proteins Download PDFInfo
- Publication number
- CN103049677A CN103049677A CN2011103152977A CN201110315297A CN103049677A CN 103049677 A CN103049677 A CN 103049677A CN 2011103152977 A CN2011103152977 A CN 2011103152977A CN 201110315297 A CN201110315297 A CN 201110315297A CN 103049677 A CN103049677 A CN 103049677A
- Authority
- CN
- China
- Prior art keywords
- protein
- little molecule
- file
- molecule
- docking
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
The invention relates to a computing method for processing interaction between small molecules and proteins. The method includes the following steps that (1) ligand file data of the proteins and the small molecules are read in; (2) atom types in ligands of the proteins and the small molecules are judged; (3) positions and angles of the ligands of the small molecules are randomly initialized; (4) a search protein algorithm is operated, coordinates and angles of the ligands of the small molecules are optimized, and a chemscore formula serves as an evaluation function; (5) the computing is ended after maximum iterative times are achieved; and (6) results such as root mean square deviation (RMSD), binding free energy delta G and coordinates of a binding site are analyzed and output. Compared with computing methods for processing the interaction between the small molecules and the proteins in prior art, the computing method for processing the interaction between the small molecules and the proteins has the advantages that when pollutants and biomacromolecules are interacted can be rapidly determined, and the like.
Description
Technical field
The present invention relates to a kind of calculating toxicology field, especially relate to a kind of computing method of processing little molecule and protein interaction.
Background technology
Growing along with human society, the human environmental problem of facing is more serious.Various workers, agricultural effluent, waste gas, waste sludge discharge enter human public environment of living, and often contain many harmful compounds in these " three wastes ".At present, there have been in the world many countries and regions the discharging of " three wastes " is limited and to forbid, the content of pollutant in the environment has been made strict restriction, made relevant legal norm and avoid its injury with the protection human body.Pollutant is that pollutant enters in the body to the hurtful process of human body, with some important protein bound process in the human body.The albumen that these are combined occupies the albumen of critical role often in people's life process.After contaminant molecule and the protein combination, two kinds of behaviors are arranged, one changes the structure of protein, and the change of structure often causes that protein function changes, and makes its forfeiture or changes original function.Under normal conditions, the existence of pollutant can affect the variation of the Secondary Structure Content of protein; They are two years old, the contaminated thing of the avtive spot of protein occupies, some functional molecules can't in conjunction with, thereby cause some to have the material of key effect to be synthesized or to transform to health, human body is these important substance that should be synthesized and suffering damage the most for want of.
The importance of pollutant and protein interaction research is particularly outstanding.Focusing on of research: at first from the aspect of macroscopic view, which kind of impact pollutant has caused to protein, and this impact is insulting health how.Secondly from microcosmic point, how the mechanism that pollutant and protein impact be.Microcosmic point combines with macroscopic aspect, to make us obtain the comprehensively visual angle thoroughly of pollutant toxicity, make people evade pollutant, and enhancing people's environmental consciousness, impel various circles of society to pay attention to the problem of environmental pollution, the dynamics that strengthens environmental renovation and stop to pollute finally makes earth environment more healthy.
Chemistry refers to by the problem in the computing method solution chemical field.Computing method in the chemistry have contained the whole bag of tricks.System according to scientist's research is different, can adopt multiple different computing method.The most frequently used computing method are molecular mechanics and quantum chemistry calculation.What the purpose of chemistry was clearer and more definite is in order to obtain macroscopical physics or the chemical property of research object.This macroscopic property can be divided into two classes: one, the static balancing character of object, the binding constant of two material effects for example, the average potential energy of an individual system or the radial distribution function of object in liquid; It two is dynamic, non-equilibrium character, for example phase transformation of object, macromolecular conformation change, the motion of little molecule in cell membrane or nanotube.
In fact, the various character of a macromolecular system are form quantum state that these macromolecular various particulates show average, and the unique channel that obtains the particulate quantum state is to solve schrodinger equation.This is because of schrodinger equation, has implied whole character of particulate.In the situation of a finite time, limited capability, it is impossible with schrodinger equation from the beginning each particulate of system being calculated, there is no need especially, so be necessary to propose a kind of more simply and effectively method, the acquisition system is character comparatively reliably.In order to address the above problem, proposed in the field that Monte Carlo simulation approach and Molecular Dynamics method apply to chemistry.To sum up, the static balancing character that computing method can the predicted object.And then obtain reliable pollutant toxicity data.
Summary of the invention
Purpose of the present invention is exactly to provide a kind of computing method of processing little molecule and protein interaction for the defective that overcomes above-mentioned prior art existence.
Purpose of the present invention can be achieved through the following technical solutions:
A kind of computing method of processing little molecule and protein interaction is characterized in that, may further comprise the steps:
(1) reads in protein and little molecule ligand file data;
(2) atomic type in judgement protein and the little molecule ligand;
(3) position of the little molecule ligand of random initializtion and angle;
(4) move the SearchProtein algorithm, optimize coordinate and the angle of little molecule ligand, the Chemscore formula is as evaluation function; The ChemScore evaluation function is that the people such as Eldridge proposed in 1997.In the program of this paper, just used the function of ChemScore function as heat-supplied.The ChemScore energy function is marked to the energy of part and protein by following formula:
ΔG
binding＝ΔG
0+ΔG
hbondS
hbond+ΔG
metalS
metal+ΔG
lipoS
lipo+ΔG
rotH
rot
(5) reach and stop after the maximum iteration time calculating;
(6) analysis result, the coordinate in RMSD (root mean-square deviation amount), docking free energy Δ G and docking site, Output rusults.
Described part file comprises the type information of type, coordinate and the key of atom.
Position and the angle of the little molecule ligand of described random initializtion are specially:
The position of little molecule ligand and angle are around the activated centre
Scope in produce at random, and search for and dock calculating by the Presearch algorithm.
Described Presearch algorithm is that the former part with protein docks with protein, finds avtive spot and obtains original docking free energy Δ G
0, read in protein and original molecule part file data, judge the atomic type in protein and the former part molecule, the position of the little molecule ligand of random initializtion and angle; Add polarity hydrogen at protein molecule, and calculate Coleman's electric charge, it is preserved the file of suffix pdbqs by name, little molecule process hydrogenation, calculated charge, and determine to save as the pdbq file behind the rotatable key; Utilize the mkdpf4 order to generate the needed lattice point Parameter File of docking, suffix is called .gpf, opens this document, grid element center is revised as the coordinate at avtive spot center; Generate the dpf file with the mkdpf4 order.
Described SearchProtein algorithm is the molecular docking of carrying out the little molecule of pollutant and protein, and obtain docking free energy Δ G, read in protein and original molecule part file data, judge the atomic type in protein and the former part molecule, the position of the little molecule ligand of random initializtion and angle; Add polarity hydrogen at protein molecule, and calculate Coleman's electric charge, it is preserved the file of suffix pdbqs by name, and little molecule is through hydrogenation, and calculated charge is determined to save as the pdbq file behind the rotatable key; Utilize the mkdpf4 order to generate the needed lattice point Parameter File of docking, suffix is called .gpf, opens this document, grid element center is revised as the coordinate at avtive spot center; Generate the dpf file with the mkdpf4 order.
Compared with prior art, the present invention has can accomplish have effect to make rapid judgement to time between pollutant and the biomacromolecule, is conducive to improving production efficiency.This key problem in technology principle is simple, suggestion for operation, and study can be used widely in all fields easily.
Embodiment
The present invention is described in detail below in conjunction with specific embodiment.
Embodiment 1
The present invention is divided into Presearch and two functional modules of SearchProtein.Mainly utilize the ANSI C Plus Plus to write, may operate under Windows and the (SuSE) Linux OS.18 of source program and header files are arranged in the routine package, and main flow process is: reading in of acceptor and ligand molecular is mainly the mol2 file layout; Acceptor and ligand molecular pre-service mainly are atomic types, appointment of the rotatable key of single shaft etc.The PreSearch program needs to prepare the presearch.txt file before operation; Then little molecule is carried out random initializtion, little molecule initialized location is around the activated centre
Scope in produce at random; Then utilize Presearch to search for and dock calculating.Calculate RMSD (root mean-square deviation amount), the docking free energy Δ G of docking and the coordinate in docking site.Set up Protein Data Bank, utilize the SearchProtein module that little molecule and large molecule are carried out reverse docking experiment.After the calculating of SearchProtein program is complete, can spanned file.File including each docking energy and the docking site coordinate.Also there is in addition file to provide respectively Δ G docks evaluation of estimate and little molecular contaminants with Δ G0 and original part the evaluation of estimate of docking.
Program has defined input file, mainly is to define acceptor molecule filename, ligand molecular filename, Initialization Center coordinate, initiation parameter, searching algorithm kind, searching algorithm parameter etc.Except acceptor molecule filename, ligand molecular filename must be specified, other parameters can be specified, and also can Use Defaults, and the usage comparison of program is easy to be easy-to-use.
The operation of program: in the ToxicitySearch program, the main variable of optimizing mainly is the three-dimensional coordinate x at the center of little molecule ligand, y and z, three Descartes's angle d of ligand molecular, β and γ, its main calculation step is: (1) reads in protein and little molecule ligand file, mainly is SYBYL mol2 file layout, contains the type of type, coordinate and the key of atom in the file; (2) atomic type in judgement protein and the little molecule ligand; (3) position of the little molecule ligand of random initializtion and angle; (4) move the SearchProtein algorithm, optimize coordinate and the angle of little molecule ligand, the Chemscore formula is as evaluation function; (5) reach maximum iteration time, stop calculating; (6) analysis result calculates RMSD, Output rusults.
Embodiment 2
The method of the protein acceptor that a kind of PFOS of searching may disturb, utilize reverse docking procedure PreSearch and reverse docking procedure SearchProtein, from self-built protein acceptor storehouse, found 4 kinds of albumen to be combined with PFOS, these albumen are phosphodiesterase 4 D catalytic domain, urokinase catalyst territory, II type carbonic anhydrase and IV type dipeptidyl peptidase, and simple analysis the situation of PFOS in these protein active sites.Its detailed process is as follows:
The PreSearch program needs to prepare the presearch.txt file before operation.
./PreSearch-p?presearch.txt-l?result.log-o?energy.txt
Calculated at work 10 times, made the evaluation of energy average.1a2c.mol2 and 1a2c-l.mol2 represents respectively the mol2 file of protein and the mol2 file of part.Whenever after finishing the calculating of 1 protein, program can generate result.log file and energy.txt file.The result.log file has at length recorded the coordinate in RMSD (root mean-square deviation amount), docking free energy and the docking site of docking.
Summed up the free energy Δ G (last row representative adds the energy because of the flexibility loss) of each docking and docked the coordinate at center, site, and this document is also as the input file of SearchProtein program.
The input file of SearchProtein is above-mentioned energy.txt file, but need to add lastrow " ligand PFOS.mol2 " in the file beginning.Need to input following order during operation:
./SearchProtein-p?energy.txt-l?result.log-o?finalenergy.txt
After the calculating of SearchProtein program is complete, can generate result.log file and finalenergy.txt file.The result.log file including each docking energy and the docking site coordinate.Finalenergy.txt then provides respectively Δ G docks evaluation of estimate and PFOS with Δ G0 and original part the evaluation of estimate of docking.
Embodiment 3
A kind of research pollutant 2, the method of 4-d and human albumin HAS interaction mechanism, as mentioning among the embodiment 1, utilize docking procedure PreSearch, find out 2,4-D may replace androgen and the position of estrogen on HSA, disturb this two kinds of hormone transportations in human body, affect its function of bringing into normal play, may make sex hormone dysequilibrium in the body, and 2, the 4-D possibility that the transportation on haemocyanin exerts an influence to thyroxine is very little.
We with the interpretation of result of Presearch docking three close molecules 2 of result, 4-D, estrogen, effect situation after androgen and the HSA docking, the activated centre that docking is chosen is the IIA avtive spot, it is worth mentioning that, in repeated multiple times calculating 2,4-D and HSA in conjunction with free energy the time, find a phenomenon special during with other molecular dockings, the convergence of docking free energy value and two values rather than a value of calculating when 2,4-D and HSA dock mutually, these two values be respectively-34.0kJ/mol and-37.4kJ/mol.And comprising estrogen, androgen all only converges on a value at interior most molecules.
We are with four kinds of molecules, five kinds of situations are placed on the figure and represent, be near the secondary structure synoptic diagram the HSA avtive spot, position when four kinds of little molecular dockings are the most stable in avtive spot, green and cyan is 2, position under the 4-D two states, blue and purple is the position of estradiol and testosterone, pink is thyroxine.Can find out, the position of two kinds of sex hormone all below the activated centre, the position of 2,4-D on the upper side, and the thyroxine molecule is longer, about running through, so in conjunction with the most stable.
The above-mentioned description to embodiment is can understand and apply the invention for the ease of those skilled in the art.The person skilled in the art obviously can easily make various modifications to these embodiment, and needn't pass through performing creative labour being applied in the General Principle of this explanation among other embodiment.Therefore, the invention is not restricted to the embodiment here, those skilled in the art should be within protection scope of the present invention for improvement and modification that the present invention makes according to announcement of the present invention.
Claims (5)
1. computing method of processing little molecule and protein interaction is characterized in that, may further comprise the steps:
(1) reads in protein and little molecule ligand file data;
(2) atomic type in judgement protein and the little molecule ligand;
(3) position of the little molecule ligand of random initializtion and angle;
(4) move the SearchProtein algorithm, optimize coordinate and the angle of little molecule ligand, the Chemscore formula is as evaluation function;
(5) reach and stop after the maximum iteration time calculating;
(6) analysis result, the coordinate in RMSD, docking free energy Δ G and docking site, Output rusults.
2. a kind of computing method of processing little molecule and protein interaction according to claim 1 is characterized in that, described part file comprises the type information of type, coordinate and the key of atom.
3. a kind of computing method of processing little molecule and protein interaction according to claim 1 is characterized in that, position and the angle of the little molecule ligand of described random initializtion are specially:
The position of little molecule ligand and angle are around the activated centre
Scope in produce at random, and search for and dock calculating by the Presearch algorithm.
4. a kind of computing method of processing little molecule and protein interaction according to claim 3 is characterized in that, described Presearch algorithm is that the former part with protein docks with protein, finds avtive spot and obtains original docking free energy Δ G
0, read in protein and original molecule part file data, judge the atomic type in protein and the former part molecule, the position of the little molecule ligand of random initializtion and angle; Add polarity hydrogen at protein molecule, and calculate Coleman's electric charge, it is preserved the file of suffix pdbqs by name, little molecule process hydrogenation, calculated charge, and determine to save as the pdbq file behind the rotatable key; Utilize the mkdpf4 order to generate the needed lattice point Parameter File of docking, suffix is called .gpf, opens this document, grid element center is revised as the coordinate at avtive spot center; Generate the dpf file with the mkdpf4 order.
5. a kind of computing method of processing little molecule and protein interaction according to claim 1, it is characterized in that, described SearchProtein algorithm is the molecular docking of carrying out the little molecule of pollutant and protein, and obtain docking free energy Δ G, read in protein and original molecule part file data, judge the atomic type in protein and the former part molecule, the position of the little molecule ligand of random initializtion and angle; Add polarity hydrogen at protein molecule, and calculate Coleman's electric charge, it is preserved the file of suffix pdbqs by name, and little molecule is through hydrogenation, and calculated charge is determined to save as the pdbq file behind the rotatable key; Utilize the mkdpf4 order to generate the needed lattice point Parameter File of docking, suffix is called .gpf, opens this document, grid element center is revised as the coordinate at avtive spot center; Generate the dpf file with the mkdpf4 order.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110315297.7A CN103049677B (en) | 2011-10-17 | 2011-10-17 | A kind of computing method processing Small molecular and protein interaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110315297.7A CN103049677B (en) | 2011-10-17 | 2011-10-17 | A kind of computing method processing Small molecular and protein interaction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103049677A true CN103049677A (en) | 2013-04-17 |
| CN103049677B CN103049677B (en) | 2015-11-25 |
Family
ID=48062311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110315297.7A Expired - Fee Related CN103049677B (en) | 2011-10-17 | 2011-10-17 | A kind of computing method processing Small molecular and protein interaction |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103049677B (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107004064A (en) * | 2014-09-30 | 2017-08-01 | 国立大学法人大阪大学 | Free energy computing device, method, program and record have the recording medium of the program |
| CN107301327A (en) * | 2017-05-17 | 2017-10-27 | 华南理工大学 | A kind of method that use computer simulation metal complex interacts with DNA |
| CN110007067A (en) * | 2019-03-11 | 2019-07-12 | 江苏理工学院 | A kind of protein molecule docking detection device |
| CN110148438A (en) * | 2019-04-12 | 2019-08-20 | 中山大学 | A kind of zinc enzyme interconnection method based on optimal geometric match |
| WO2020168507A1 (en) * | 2019-02-21 | 2020-08-27 | 深圳晶泰科技有限公司 | Molecular docking cloud computing process control method |
| CN111613275A (en) * | 2020-05-26 | 2020-09-01 | 中国海洋大学 | Drug molecular dynamics result analysis method based on rmsd multi-feature |
| CN111933222A (en) * | 2020-08-04 | 2020-11-13 | 云南中烟工业有限责任公司 | Compound cooling degree judging method |
| CN114627971A (en) * | 2022-03-18 | 2022-06-14 | 北京有竹居网络技术有限公司 | Data processing method and device for solid-state systems |
| WO2022227613A1 (en) * | 2021-04-27 | 2022-11-03 | 中国科学院深圳先进技术研究院 | Method and system for dynamically analyzing interaction between protein and small molecules, and computer-readable carrier |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030009291A1 (en) * | 2000-09-12 | 2003-01-09 | Ernesto Freire | Structural prediction of allosterism |
| CN101470776A (en) * | 2007-06-27 | 2009-07-01 | 弗·哈夫曼-拉罗切有限公司 | Systems and methods for mapping binding site volumes in macromolecules |
| CN102156823A (en) * | 2011-02-18 | 2011-08-17 | 复旦大学 | Method for screening compound with targeted action on inactive conformation of protein kinase |
-
2011
- 2011-10-17 CN CN201110315297.7A patent/CN103049677B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030009291A1 (en) * | 2000-09-12 | 2003-01-09 | Ernesto Freire | Structural prediction of allosterism |
| CN101470776A (en) * | 2007-06-27 | 2009-07-01 | 弗·哈夫曼-拉罗切有限公司 | Systems and methods for mapping binding site volumes in macromolecules |
| CN102156823A (en) * | 2011-02-18 | 2011-08-17 | 复旦大学 | Method for screening compound with targeted action on inactive conformation of protein kinase |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107004064B (en) * | 2014-09-30 | 2020-09-29 | 国立大学法人大阪大学 | Free energy calculation device, method, program, and recording medium having the program recorded thereon |
| CN107004064A (en) * | 2014-09-30 | 2017-08-01 | 国立大学法人大阪大学 | Free energy computing device, method, program and record have the recording medium of the program |
| CN107301327A (en) * | 2017-05-17 | 2017-10-27 | 华南理工大学 | A kind of method that use computer simulation metal complex interacts with DNA |
| WO2020168507A1 (en) * | 2019-02-21 | 2020-08-27 | 深圳晶泰科技有限公司 | Molecular docking cloud computing process control method |
| CN110007067A (en) * | 2019-03-11 | 2019-07-12 | 江苏理工学院 | A kind of protein molecule docking detection device |
| CN110148438A (en) * | 2019-04-12 | 2019-08-20 | 中山大学 | A kind of zinc enzyme interconnection method based on optimal geometric match |
| CN110148438B (en) * | 2019-04-12 | 2023-03-21 | 中山大学 | Zinc enzyme docking method based on optimal geometric matching |
| CN111613275A (en) * | 2020-05-26 | 2020-09-01 | 中国海洋大学 | Drug molecular dynamics result analysis method based on rmsd multi-feature |
| CN111933222A (en) * | 2020-08-04 | 2020-11-13 | 云南中烟工业有限责任公司 | Compound cooling degree judging method |
| CN111933222B (en) * | 2020-08-04 | 2024-05-07 | 云南中烟工业有限责任公司 | Compound cooling degree discrimination method |
| WO2022227613A1 (en) * | 2021-04-27 | 2022-11-03 | 中国科学院深圳先进技术研究院 | Method and system for dynamically analyzing interaction between protein and small molecules, and computer-readable carrier |
| CN114627971A (en) * | 2022-03-18 | 2022-06-14 | 北京有竹居网络技术有限公司 | Data processing method and device for solid-state systems |
| CN114627971B (en) * | 2022-03-18 | 2023-10-31 | 北京有竹居网络技术有限公司 | Data processing method and device for solid system |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103049677B (en) | 2015-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103049677A (en) | Computing method for processing interaction between small molecules and proteins | |
| Zong et al. | First assessment of NO x sources at a regional background site in North China using isotopic analysis linked with modeling | |
| Chu et al. | Air pollutant correlations in China: secondary air pollutant responses to NO x and SO2 control | |
| Gu et al. | Reduction in NO x emission trends over China: Regional and seasonal variations | |
| Hurteau et al. | Projected effects of climate and development on California wildfire emissions through 2100 | |
| Liu et al. | Tracking daily concentrations of PM2. 5 chemical composition in China since 2000 | |
| Zhao et al. | East China plains: A “basin” of ozone pollution | |
| Elliott et al. | Nitrogen isotopes as indicators of NO x source contributions to atmospheric nitrate deposition across the midwestern and northeastern United States | |
| Li et al. | “New” reactive nitrogen chemistry reshapes the relationship of ozone to its precursors | |
| Henze et al. | Spatially refined aerosol direct radiative forcing efficiencies | |
| Hudait et al. | Sink or swim: ions and organics at the ice–air interface | |
| Wang et al. | Sensitivities of ozone air pollution in the Beijing–Tianjin–Hebei area to local and upwind precursor emissions using adjoint modeling | |
| Lv et al. | Properties and atmospheric implication of methylamine–sulfuric acid–water clusters | |
| Malmström et al. | Modeling expected solute concentration in randomly heterogeneous flow systems with multicomponent reactions | |
| Erdakos et al. | Predicting the effects of nanoscale cerium additives in diesel fuel on regional-scale air quality | |
| Darvas et al. | Competitive adsorption of surfactants and polymers at the free water surface. A computer simulation study of the sodium dodecyl Sulfate− Poly (ethylene oxide) system | |
| Tang et al. | Unregulated emissions from a heavy-duty diesel engine with various fuels and emission control systems | |
| Schroth et al. | Lead sequestration and species redistribution during soil organic matter decomposition | |
| Liu et al. | Nitrogen isotope differences between major atmospheric NO y species: Implications for transformation and deposition processes | |
| Choi et al. | Apportioning and locating nonmethane hydrocarbon sources to a background site in Korea | |
| Koplitz et al. | Changes in ozone chemical sensitivity in the United States from 2007 to 2016 | |
| Yau et al. | Quantifying the impact of anthropogenic atmospheric nitrogen deposition on the generation of hypoxia under future emission scenarios in Chinese coastal waters | |
| Li et al. | Impacts of additional HONO sources on O3 and PM2. 5 chemical coupling and control strategies in the Beijing–Tianjin–Hebei region of China | |
| Gingerich et al. | Air emissions damages from municipal drinking water treatment under current and proposed regulatory standards | |
| Moosavi et al. | Carbon dioxide in monoethanolamine: Interaction and its effect on structural and dynamic properties by molecular dynamics simulation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20151125 Termination date: 20171017 |