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In Silico Drug Exploration and Discovery Using DrugBank
Publication Name:
Current Protocols in Bioinformatics
Unit Number:
UNITÂ 14.4
DOI:
10.1002/0471250953.bi1404s18
Print Publication Date:
June, 2007
Online Posting Date:
June, 2007 Abstract
DrugBank is a fully curated drug and drug target database that contains information on nearly 5000 drugs, including >1200 FDA-approved small molecule and biotech drugs as well as >3200 experimental drugs. Additionally, more than 14,000 protein or drug target sequences are linked to these drug entries. DrugBank is primarily focused on providing both the query/search tools and the biophysical data needed to facilitate drug discovery and drug development. This unit provides readers with a detailed description of how to effectively use the DrugBank database and how to navigate through the DrugBank Web site. It also provides specific examples of how to find chemical homologs of potential drug leads and how to identify potential drug targets from newly sequenced pathogens. The intent of this unit is to give readers some introduction into the field of cheminformatics (the study of chemical information) and to show how cheminformatics can be seamlessly integrated into the field of bioinformatics.
Keywords: Database; bioinformatics; drug; chemical; drug target
Table of Contents
- Unit Introduction
- Basic Protocol 1: Navigating the DrugBank Web Site
- Basic Protocol 2: Chemical Structure Similarity Searching
- Basic Protocol 3: In Silico Drug Target Identification
- Guidelines for Understanding Results
- Commentary
- Literature Cited
- Figures
- Tables
Figures
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Figure 14.4.1Screen shot of the DrugBank home page. At the top of the page is a menu bar (blue on screen) containing eight menu choices (in white). Users can navigate through DrugBank using this menu bar. Details of how to use, contact, and reference DrugBank are given in the central text window. -
Figure 14.4.2A screen shot of a Search DrugBank for query output for the word “tricyclic.” The drug names on the left side of the table are hyperlinked. -
Figure 14.4.3A screen shot of the DrugCard for desipramine, a tricyclic antidepressant. -
Figure 14.4.4A 2-D image of the structure of desipramine as displayed using the ChemSketch Java applet. The image may be manipulated for different display purposes. -
Figure 14.4.5An image of the 3-D structure of desipramine as displayed using the WebMol Java applet. Users may manipulate the image for better viewing or further analysis. -
Figure 14.4.6Details of the SNP (single nucleotide polymorphism) drug target information contained in the DrugCard for desipramine. -
Figure 14.4.7A screen shot of the DrugBank Browser. Note the tabular format and the sorting/display tools at the top of the Browser page. -
Figure 14.4.8A screen shot of the DrugBank Browser set to display biotech (i.e., protein) drugs. -
Figure 14.4.9A screen shot of the DrugBank Browser set to display biotech drugs sorted by molecule weight (from smallest to largest). -
Figure 14.4.10A screen shot of the PharmaBrowse browsing/navigation page. Note the hyperlinked list of drug categories and general indications. -
Figure 14.4.11A screen shot of the Text Query window. This permits more complex text queries than what is available through the default Search tool. -
Figure 14.4.12A screen shot of the Data Extractor window. The Data Extractor supports advanced SQL-like searches through many different data fields. -
Figure 14.4.13A screen shot of the Data Extractor query window. Users are required to fill in the text boxes using the suggested characters or formats. -
Figure 14.4.14A screen shot of the output from a Data Extractor Query aimed at finding all drugs less than 300 Da with LogPs between 3.4 and 4.2 that are antidepressants. -
Figure 14.4.15A screen shot of DrugBank's Download page. -
Figure 14.4.16A screen shot of the ChemQuery window with the ACD ChemSketch Java applet at the center. This is where the query chemical structures can be drawn. -
Figure 14.4.17A screen shot of the ChemSketch applet with the template library window placed above the drawing palette. -
Figure 14.4.18A screen shot of the ChemSketch applet with a heptacyclic ring placed at the center of the palette. -
Figure 14.4.19A screen shot of the partially completed tricyclic structure of the sea snail product. -
Figure 14.4.20A screen shot of the complete chemical structure of the sea snail product. This is the query structure used by ChemQuery. -
Figure 14.4.21A screen shot of the MOL file generated by the ChemQuery conversion utility. -
Figure 14.4.22A screen shot of the similar structures found using the ChemQuery search tool. -
Figure 14.4.23A screen shot of the table generated when the Search for Similar Structures button is pressed for desipramine. -
Figure 14.4.24A screen shot of the SeqSearch window. Note the standard BLAST query interface. -
Figure 14.4.25A screen shot of the Web site listing the 16 protein sequences for the newly sequenced retrovirus. -
Figure 14.4.26A screen shot of the SeqSearch window with all 16 retroviral protein sequences pasted into the text box. -
Figure 14.4.27A screen shot of the SeqSearch output for the second sequence (Sequence 2) in the retroviral proteome. Note the drug names and hyperlinks in the output.
Literature Cited
| Literature Cited | |
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| Wishart, D.S., Knox, C., Guo, A., Shrivastava, S., Hassanali, M., Stothard, P., and Woolsey, J. 2006. DrugBank: A comprehensive resource for in silico drug discovery and exploration. Nucl. Acids. Res. 34:D668-D672. | |
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| Internet Resources | |
| http://redpoll.pharmacy.ualberta.ca/drugbank/ | |
| DrugBank Web site | |
| http://pubchem.ncbi.nlm.nih.gov/ | |
| PubChem Web site | |
| http://xin.cz3.nus.edu.sg/group/cjttd/TTD_ns.asp | |
| TTD Web site | |
| http://www.genome.jp/kegg/drug/ | |
| KEGG drug database Web site | |
| http://www.cmpharm.ucsf.edu/~walther/webmol.html | |
| WebMol Web site | |
| http://tubic.tju.edu.cn/deg/ | |
| Database of Essential Genes | |
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