Computation in BioInformatics. Группа авторов
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target [30]. The drug target may be a protein or enzyme. Virtual screening approaches are mainly of two types: structure-based and ligand-based. In structure-based virtual screening, molecular docking studies help in screening of target protein against ligands/compounds that are present in chemical libraries. The process of docking is usually based on the functional scores and binding strength of the compound with its target. Virtual screening uses computational programs to evaluate huge libraries of compounds automatically [31]. It is an accurate method allowing the researches to obtain an authenticated structure which might be useful as a drug after further validations. Because of this, virtual screening is necessary and has become an important part of drug discovery process [18].
MTiOpenScreen: This approach involves docking of small molecules and virtual screening. The screening can be done in one run which can be up to 5,000 small molecules in different databases. The run can also be up to 10,000 molecules selected among 15,000 compounds that are prepared to be docked which is provided at MTiOpenScreen. The web server can be obtained from http://bioserv.rpbs.univ-parisdiderot.fr/services/MTiOpenScreen/.
ICM-VLS: ICM Virtual Ligand Screening (VLS) is a combination of internal coordinate docking methodology with a sophisticated global optimization scheme. Its accuracy and fast potentials have led to an efficient virtual screening methodology in which ligands are fully and continuously flexible. It can be accessed at http://www.molsoft.com/vls.html.
1.2.5 Molecular Docking
Molecular docking is a computer simulation methodology which predicts the binding affinity of the target protein with the ligand at the atomistic level. The most important goal of molecular docking studies is to predict the binding conformation of protein-ligand and to estimate its interaction. It is also one of the main tools for virtual screening procedures, where a library of several compounds is “docked” against one drug target returning the best hit. Identifying the active site of the target protein where the ligand will bind is the first important step which needs to be performed before docking. This can be performed using programs like Q-SiteFinder, LigA Site, Meta Pocket, and CASTp [32]. A molecular docking study where the process of docking is performed without predicting the active site is referred as “Blind Docking” [33]. Here, Tables 1.2 and 1.3 show some of the most common Molecular docking software programs along with their specifications.
AutoDock: It is an automated program to predict ligand and protein (bio-macromolecular targets) interactions. With recent advancement in bimolecular, X-ray crystallography is helping to provide structural information of complex bio-molecules such as protein and nucleic acids. The structures can be taken/downloaded and can be used as targets for new drug molecules in controlling diseases and disorders of human, animal, and plant and understanding of fundamental aspects of biology [41]. It can be downloaded from http://www.scripps.edu/olson/forli/autodock_flex_rings.html (accessed 12.12.16).
GOLD: Genetic Optimization for Ligand Docking is a genetic algorithm which provides docking of flexible ligand and a protein with flexible hydroxyl groups. The software uses a scoring function that is based on favorable conformations found in Cambridge Structural Database. The speed of GOLD and the reliability of its predictions depend on the control of different values of the genetic algorithm parameters. It provides reliable results both protein and ligand (http://www.ccdc.cam.ac.uk/Solutions/GoldSuite/Pages/GOLD.aspx) (accessed 20.12.16).
Table 1.2 The list of molecular docking softwares is represented in tabular form.
| S. no. | Name of software | Description | Reference |
| 1 | AutoDock | It performs automated docking of flexible ligands to macromolecules. | [34] |
| 2 | DockVision | It performs Monte Carlo, Genetic Algorithm, and database screening docking algorithms. | [35, 36] |
| 3 | GOLD | It helps in identifying correct binding modes of the active target molecules. | [37] |
| 4 | Docking Server | It provides a web-based interface for the molecular docking of protein and ligand. | [38] |
| 5 | SwissDock | It is a protein ligand server that is accessed through ExPASy. | [39] |
| 6 | CombiBUILD | It is a structure-based drug design program which helps in designing of combinatorial libraries. | [37] |
| 7 | QM Polarized Ligand Docking | It performs the function of both Glide and Q-Site applications of Schrodinger Suit. | [40] |
| 8 | Docking Server | It provides a web-based, easy to use interface for the molecular docking of protein and ligand. | [34] |
| 10 | Click2Drug | It is a protein ligand server that is accessed through ExPASy. | http://www.click2drug.org/ |
Table 1.3 The list of molecular docking tools is represented in tabular form.
| Tool | Brief description with uses |
| BLAST | Basic local alignment search tool; used for sequencing of DNA and protein. |
| RasMol | Raster molecule tool; used for molecular visualization of RNA/DNA and protein. |
| Discovery studio | Software; used for modeling and simulation. |
| Pub Med | Free search engine; used for searching matter related to medical and life sciences. |
| PDB | Protein Data Bank; used to collect information related to macromolecule. |
| Chem Draw |
They are a part of the Chem office |