CN109637673A - A kind of drug virtual screening method - Google Patents
A kind of drug virtual screening method Download PDFInfo
- Publication number
- CN109637673A CN109637673A CN201811550797.7A CN201811550797A CN109637673A CN 109637673 A CN109637673 A CN 109637673A CN 201811550797 A CN201811550797 A CN 201811550797A CN 109637673 A CN109637673 A CN 109637673A
- Authority
- CN
- China
- Prior art keywords
- compound
- screened
- template molecule
- screening method
- virtual screening
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 24
- 239000003814 drug Substances 0.000 title claims abstract description 20
- 229940079593 drug Drugs 0.000 title claims abstract description 20
- 238000003041 virtual screening Methods 0.000 title claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 239000000126 substance Substances 0.000 claims abstract description 14
- 230000000694 effects Effects 0.000 claims description 7
- 230000006870 function Effects 0.000 claims description 6
- 230000001413 cellular effect Effects 0.000 claims description 4
- 238000005452 bending Methods 0.000 claims description 3
- 230000009881 electrostatic interaction Effects 0.000 claims description 3
- 238000013215 result calculation Methods 0.000 claims description 3
- 238000005411 Van der Waals force Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 238000012216 screening Methods 0.000 abstract description 20
- 239000003446 ligand Substances 0.000 abstract description 8
- 238000007877 drug screening Methods 0.000 abstract description 7
- 102000004169 proteins and genes Human genes 0.000 abstract description 4
- 108090000623 proteins and genes Proteins 0.000 abstract description 4
- 230000001133 acceleration Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 102000016912 Aldehyde Reductase Human genes 0.000 description 1
- 108010053754 Aldehyde reductase Proteins 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H70/00—ICT specially adapted for the handling or processing of medical references
- G16H70/40—ICT specially adapted for the handling or processing of medical references relating to drugs, e.g. their side effects or intended usage
Landscapes
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Medical Informatics (AREA)
- Primary Health Care (AREA)
- Public Health (AREA)
- Information Retrieval, Db Structures And Fs Structures Therefor (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a kind of drug virtual screening methods, include the following steps, S1: edit the chemical structure of template molecule；S2: according to molecular force field to step S1The chemical structure of middle template molecule generates three-dimensional conformation；S3: in corresponding step S2Molecular force field in three-dimensional coordinate is generated to the chemical structure of each compound to be screened；S4: using Gaussian function to respectively to template molecule and each compound to be screened molecular shape and pharmacophore express；S5: it will be analyzed to the three-dimensional conformation of template molecule and the three-dimensional conformation of each compound to be screened, comprehensively consider the molecular shape and pharmacophore of template molecule and each compound to be screened.Since smaller ligand is played a role by three-dimensional conformation and protein binding, by constructing three-dimensional conformation, the combination of fit shapes and pharmacophore carries out drug screening, and for the selection result closer to actual conditions, the screening structure of drug is more accurate.
Description
Technical field
The present invention relates to the screenings of compound, more specifically to a kind of drug virtual screening method.
Background technique
Drug virtual screening method includes structure-based drug screening and the drug screening two major classes based on ligand.It is based on
The drug screening of structure by protein structure and scoring functions accuracy due to being limited, the method for the drug screening based on ligand
Since principle is relatively easy, breakneck acceleration is very fast and is widely applied.Tradition is mainly based upon based on the screening technique of ligand
The screening technique of two-dimensional topology similarity, screening precision are lower.Therefore a kind of screening drug virtual screening with high accuracy is needed
Method.
Summary of the invention
In view of the above drawbacks of the prior art, the purpose of the present invention is to provide a kind of drug virtual screenings that accuracy is high
Method.
To achieve the above object, the technical solution adopted in the present invention is as follows:
A kind of drug virtual screening method, includes the following steps,
S1: edit the chemical structure of template molecule；
S2: according to molecular force field to step S1The chemical structure of middle template molecule generates three-dimensional conformation；
S3: in corresponding step S2Molecular force field in three-dimensional coordinate is generated to the chemical structure of each compound to be screened；
S4: using Gaussian function to respectively to template molecule and each compound to be screened molecular shape and pharmacophore carry out
Expression；
S5: it will analyze, comprehensively consider to the three-dimensional conformation of template molecule and the three-dimensional conformation of each compound to be screened
The molecular shape and pharmacophore of template molecule and each compound to be screened.
Preferably, step S5Using Golang language.
Preferably, step S2And S3In molecular force field include key stretch energy, bond angle bending energy, dihedral angle distortion energy, Fan De
Hua Li and electrostatic interaction.
Preferably, according to S5Analysis result calculation similarity, each to be screenedization of the correspondence that similarity is reached into preset threshold
Close the output of object data.
Preferably, the relatively independent setting of preset threshold when comparing with three-dimensional conformation is compared using two-dimensional coordinate.
Preferably, after each compound data output to be screened of the correspondence for similarity being reached preset threshold, matching output number
Corresponding compound carries out the screening of entity activity index in.
Preferably, the type of entity is at least one of molecular level, cellular level and animal level.
Compared with prior art, the invention has the following advantages:
Since smaller ligand is played a role by three-dimensional conformation and protein binding, by constructing three-dimensional conformation, cooperation
The combination of shape and pharmacophore carries out drug screening, and for the selection result closer to actual conditions, the screening structure of drug is more accurate.
In the following, being described further in conjunction with specific embodiment to the present invention.
Specific embodiment
Below in conjunction with embodiment of the present invention, the technical solution in embodiment of the present invention is carried out clearly and completely
Description, it is clear that described embodiment is only some embodiments of the invention, rather than whole embodiments.Base
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts all
Other embodiments shall fall within the protection scope of the present invention.
In the description of the present invention, it should be noted that term " center ", "upper", "lower", "left", "right", "vertical",
The orientation or positional relationship of the instructions such as "horizontal", "inner", "outside", is merely for convenience of description of the present invention and simplification of the description, without
It is that the device of indication or suggestion meaning or element must have a particular orientation, be constructed and operated in a specific orientation, therefore not
It can be interpreted as limitation of the present invention；Term "horizontal", " second ", " third " are used for description purposes only, and should not be understood as referring to
Show or imply relative importance；Furthermore unless specifically defined or limited otherwise, term " installation ", " connected ", " connection " should be done
It broadly understood, for example, it may be being fixedly connected, may be a detachable connection, or be integrally connected；It can be mechanical connection,
It is also possible to be electrically connected；It can be directly connected, can also can be inside two elements indirectly connected through an intermediary
Connection.For the ordinary skill in the art, can be understood with concrete condition above-mentioned term in the present invention specifically contain
Justice.
A kind of drug virtual screening method, includes the following steps,
S1: edit the chemical structure of template molecule；
S2: according to molecular force field to step S1The chemical structure of middle template molecule generates three-dimensional conformation；
S3: in corresponding step S2Molecular force field in three-dimensional coordinate is generated to the chemical structure of each compound to be screened；
S4: using Gaussian function to respectively to template molecule and each compound to be screened molecular shape and pharmacophore carry out
Expression；
S5: it will analyze, comprehensively consider to the three-dimensional conformation of template molecule and the three-dimensional conformation of each compound to be screened
The molecular shape and pharmacophore of template molecule and each compound to be screened.
Working principle: in use, the chemical structure of template molecule and the chemical structure of each compound to be screened are being divided respectively
Generate corresponding three-dimensional conformation in the sub- field of force, then by template molecule and the corresponding three-dimensional conformation combination shape of each compound to be screened
It is compared with pharmacophore, since smaller ligand is played a role by three-dimensional conformation and protein binding, then utilizing height
This function expresses the shape and pharmacophore of template molecule and each compound to be screened, and pharmacophore is living to a series of biologies
Property molecule summary, summarize to activity rise most recast structure feature.Pharmacophore can be folded by stable conformation and molecule
It closes to simulate the activity conformation of ligand molecular, can infer and explain possible effect mould between receptor and ligand molecular accordingly
Formula, the more compound reality of obtained structure, the structure of screening is more accurate, is expressed using Gaussian function, and difficulty in computation is reduced,
Improve screening precision and breakneck acceleration.
Molecular force field specifically includes the flexible energy of key, bond angle bending energy and dihedral angle distortion energy, nonbonding phase of independent energy item
Interaction includes Van der Waals force and electrostatic interaction.
Step S5Using Golang language.
Using the multi-thread concurrent operation of Golang language, data processing amount is big, and screening is quick.
According to S5Analysis result calculation similarity, each compound data to be screened of the correspondence that similarity is reached into preset threshold
Output.
By preset threshold, screening compounds are treated before carrying out entity screening and are screened, it is higher for similarity
Compound to be screened, reduce screening range, and then reduce entity screening workload and cost, shorten drug screening when
Between, accelerate the discovery of drug.
The relatively independent setting of preset threshold when comparing with three-dimensional conformation is compared using two-dimensional coordinate.
Three-dimensional conformation generally carries out the whole of molecule and compares, and two-dimensional coordinate is conducive to the progress of the part-structure in molecular structure
It compares, corresponding comparison method is selected according to actual comparison demand, it is accurate that two kinds of comparison method combinations are conducive to comparison structure
The raising of property.
After each compound data output to be screened of the correspondence that similarity is reached preset threshold, match corresponding in output data
Compound carry out entity activity index screening.
Entity activity index refers to the indexs such as including IC50, EC50, Ki and Kd.
By the result of virtual screening using the screening with entity, screening process is improved, further verifies virtual screening and reality
The accuracy of body screening, establishes database convenient for subsequent, and the selection result is directly applied to reality, needn't be screened again.
The type of entity is at least one of molecular level, cellular level and animal level.
Molecular level corresponds to molecular target, such as aldose reductase；Cellular level corresponds to cell line, such as 3T3cells；
Animal level corresponds to animal, such as mouse.
Can be had and template point according to the Structure Selection of template molecule using drug virtual screening method of the present invention screening
The selection result is applied to different entity types and expressed, had a wide range of application by the compound of the similar structure of son.
It will be apparent to those skilled in the art that can technical solution and design as described above, make various other phases
The change and deformation answered, and all these change and deformation all should belong to the claims in the present invention protection scope it
It is interior.
Claims (7)
1. a kind of drug virtual screening method, which is characterized in that include the following steps,
S1: edit the chemical structure of template molecule；
S2: according to molecular force field to step S1Described in template molecule chemical structure generate three-dimensional conformation；
S3: in corresponding step S2Molecular force field in three-dimensional coordinate is generated to the chemical structure of each compound to be screened；
S4: using Gaussian function to the molecular shape and pharmacophore respectively to the template molecule and each compound to be screened
It is expressed；
S5: it will be analyzed to the three-dimensional conformation of template molecule and the three-dimensional conformation of each compound to be screened, comprehensively consider institute
State the molecular shape and pharmacophore of template molecule and each compound to be screened.
2. drug virtual screening method according to claim 1, which is characterized in that step S5Using Golang language.
3. drug virtual screening method according to claim 1, which is characterized in that step S2And S3In the molecular force
Field includes the flexible energy of key, bond angle bending energy, dihedral angle distortion energy, Van der Waals force and electrostatic interaction.
4. drug virtual screening method according to claim 1, which is characterized in that according to S5Analysis result calculation similarity,
The correspondence that similarity is reached into preset threshold each compound data output to be screened.
5. drug virtual screening method according to claim 4, which is characterized in that compared and three-dimensional structure using two-dimensional coordinate
The relatively independent setting of preset threshold when as comparing.
6. drug virtual screening method according to claim 4, which is characterized in that similarity is reached to pair of preset threshold
After answering each compound data output to be screened, the sieve that corresponding compound in output data carries out entity activity index is matched
Choosing.
7. drug virtual screening method according to claim 6, which is characterized in that the type of the entity is molecular water
At least one of flat, cellular level and animal level.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811550797.7A CN109637673A (en) | 2018-12-18 | 2018-12-18 | A kind of drug virtual screening method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811550797.7A CN109637673A (en) | 2018-12-18 | 2018-12-18 | A kind of drug virtual screening method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109637673A true CN109637673A (en) | 2019-04-16 |
Family
ID=66075138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811550797.7A Pending CN109637673A (en) | 2018-12-18 | 2018-12-18 | A kind of drug virtual screening method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109637673A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115762634A (en) * | 2022-12-29 | 2023-03-07 | 三亚希诺科技有限公司 | Virtual screening method of antitumor drug, CDK5 drug and antitumor drug |
| CN117789859A (en) * | 2023-12-28 | 2024-03-29 | 苏州腾迈医药科技有限公司 | Molecular force field display method, device and medium |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050009093A1 (en) * | 2000-12-15 | 2005-01-13 | Ola Engkvist | Focussing of compound libraries using atomic electrotopological values |
| WO2007004643A1 (en) * | 2005-07-04 | 2007-01-11 | Nippon Zoki Pharmaceutical Co., Ltd. | Molecule superimposition method utilized together with three-dimensional structure activity correlation method |
| CN102799779A (en) * | 2012-07-16 | 2012-11-28 | 中山大学 | Molecular volume calculating method and shape comparing method of two molecules |
| CN107657146A (en) * | 2017-09-20 | 2018-02-02 | 广州市爱菩新医药科技有限公司 | Drug molecule comparative approach based on three-dimensional minor structure |
| CN108875298A (en) * | 2018-06-07 | 2018-11-23 | 北京计算科学研究中心 | Based on the matched drug screening method of molecular shape |
-
2018
- 2018-12-18 CN CN201811550797.7A patent/CN109637673A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050009093A1 (en) * | 2000-12-15 | 2005-01-13 | Ola Engkvist | Focussing of compound libraries using atomic electrotopological values |
| WO2007004643A1 (en) * | 2005-07-04 | 2007-01-11 | Nippon Zoki Pharmaceutical Co., Ltd. | Molecule superimposition method utilized together with three-dimensional structure activity correlation method |
| CN102799779A (en) * | 2012-07-16 | 2012-11-28 | 中山大学 | Molecular volume calculating method and shape comparing method of two molecules |
| CN107657146A (en) * | 2017-09-20 | 2018-02-02 | 广州市爱菩新医药科技有限公司 | Drug molecule comparative approach based on three-dimensional minor structure |
| CN108875298A (en) * | 2018-06-07 | 2018-11-23 | 北京计算科学研究中心 | Based on the matched drug screening method of molecular shape |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115762634A (en) * | 2022-12-29 | 2023-03-07 | 三亚希诺科技有限公司 | Virtual screening method of antitumor drug, CDK5 drug and antitumor drug |
| CN117789859A (en) * | 2023-12-28 | 2024-03-29 | 苏州腾迈医药科技有限公司 | Molecular force field display method, device and medium |
| CN117789859B (en) * | 2023-12-28 | 2024-09-06 | 苏州腾迈医药科技有限公司 | Molecular force field display method, device and medium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112201313B (en) | Automatic small molecule drug screening method and computing equipment | |
| Jaitly et al. | Robust algorithm for alignment of liquid chromatography− mass spectrometry analyses in an accurate mass and time tag data analysis pipeline | |
| Long et al. | Nonlinear machine learning of patchy colloid self-assembly pathways and mechanisms | |
| Stahl et al. | A validation study on the practical use of automated de novo design | |
| CN109637596B (en) | Drug target prediction method | |
| EP1957243A4 (en) | PROCESS FOR SHAPING AND NAVIGATING A MOBILE ROBOT THROUGH AN ARTIFICIAL WAYPOINT AND A LOCAL COORDINATE | |
| US10001489B2 (en) | Method for constructing a novel affinity peptide library for binding immunoglobulin G based on a protein affinity model of protein A | |
| CN103336855A (en) | Two-dimensional irregular layout method based on multi-subpopulation particle swarm optimization | |
| CN109637673A (en) | A kind of drug virtual screening method | |
| Zhang et al. | Equipocket: an e (3)-equivariant geometric graph neural network for ligand binding site prediction | |
| Kasahara et al. | Comprehensive classification and diversity assessment of atomic contacts in protein–small ligand interactions | |
| CN107526939B (en) | Rapid alignment method for small molecular structure | |
| CN106295243B (en) | A method for predicting the structure of protein-RNA complexes | |
| CN109002690A (en) | The method for predicting mutating acid side-chain structure by the building field of force CHARMM ROTAMERS | |
| CN108984833A (en) | A kind of tire enters mould angle analysis method and device | |
| Duan et al. | A light deformable multi-scale defect detection model for irregular small defects with complex background | |
| WO2002091287A3 (en) | Determining structures by performing comparisons between molecular replacement results for multiple different biomolecules | |
| Sharma et al. | An In-Silico Approach for Analysing the interplay of Hepatitis B viral X protein with Human Adaptin protein | |
| Newton et al. | Constraint guided beta-sheet refinement for protein structure prediction | |
| McKnight et al. | Estimating loop length from CryoEM images at medium resolutions | |
| Hunge et al. | Advancing Drug Discovery through a Deep Learning-Based Protein-Ligand Interaction Prediction Tool | |
| Hashmi et al. | idDock+: Integrating Machine Learning in Probabilistic Search for Protein–Protein Docking | |
| KR102606633B1 (en) | Method, computing device and computer program for matching scan data based on driving environment feature of autonomous vehicle | |
| Soni et al. | COCONUT: An analysis of coiled-coil regions in proteins | |
| Bui et al. | Investigating intracellular SIRT1 regulation mechanisms using molecular dynamics simulations and machine learning |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190416 |
|
| RJ01 | Rejection of invention patent application after publication |