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        In Silico Drug Exploration and Discovery Using DrugBank

        互联网

        1087
        • Abstract
        • Table of Contents
        • Figures
        • Literature Cited

        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

             
         
        GO TO THE FULL PROTOCOL:
        PDF or HTML at Wiley Online Library

        Table of Contents

        • 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
             
         
        GO TO THE FULL PROTOCOL:
        PDF or HTML at Wiley Online Library

        Materials

         
        GO TO THE FULL PROTOCOL:
        PDF or HTML at Wiley Online Library

        Figures

        •   Figure Figure 14.4.1 Screen 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.
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        •   Figure Figure 14.4.2 A 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.
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        •   Figure Figure 14.4.3 A screen shot of the DrugCard for desipramine, a tricyclic antidepressant.
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        •   Figure Figure 14.4.4 A 2‐D image of the structure of desipramine as displayed using the ChemSketch Java applet. The image may be manipulated for different display purposes.
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        •   Figure Figure 14.4.5 An 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.
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        •   Figure Figure 14.4.6 Details of the SNP (single nucleotide polymorphism) drug target information contained in the DrugCard for desipramine.
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        •   Figure Figure 14.4.7 A screen shot of the DrugBank Browser. Note the tabular format and the sorting/display tools at the top of the Browser page.
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        •   Figure Figure 14.4.8 A screen shot of the DrugBank Browser set to display biotech (i.e., protein) drugs.
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        •   Figure Figure 14.4.9 A screen shot of the DrugBank Browser set to display biotech drugs sorted by molecule weight (from smallest to largest).
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        •   Figure Figure 14.4.10 A screen shot of the PharmaBrowse browsing/navigation page. Note the hyperlinked list of drug categories and general indications.
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        •   Figure Figure 14.4.11 A screen shot of the Text Query window. This permits more complex text queries than what is available through the default Search tool.
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        •   Figure Figure 14.4.12 A screen shot of the Data Extractor window. The Data Extractor supports advanced SQL‐like searches through many different data fields.
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        •   Figure Figure 14.4.13 A screen shot of the Data Extractor query window. Users are required to fill in the text boxes using the suggested characters or formats.
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        •   Figure Figure 14.4.14 A 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.
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        •   Figure Figure 14.4.15 A screen shot of DrugBank's Download page.
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        •   Figure Figure 14.4.16 A 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.
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        •   Figure Figure 14.4.17 A screen shot of the ChemSketch applet with the template library window placed above the drawing palette.
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        •   Figure Figure 14.4.18 A screen shot of the ChemSketch applet with a heptacyclic ring placed at the center of the palette.
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        •   Figure Figure 14.4.19 A screen shot of the partially completed tricyclic structure of the sea snail product.
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        •   Figure Figure 14.4.20 A screen shot of the complete chemical structure of the sea snail product. This is the query structure used by ChemQuery.
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        •   Figure Figure 14.4.21 A screen shot of the MOL file generated by the ChemQuery conversion utility.
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        •   Figure Figure 14.4.22 A screen shot of the similar structures found using the ChemQuery search tool.
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        •   Figure Figure 14.4.23 A screen shot of the table generated when the Search for Similar Structures button is pressed for desipramine.
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        •   Figure Figure 14.4.24 A screen shot of the SeqSearch window. Note the standard BLAST query interface.
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        •   Figure Figure 14.4.25 A screen shot of the Web site listing the 16 protein sequences for the newly sequenced retrovirus.
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        •   Figure Figure 14.4.26 A screen shot of the SeqSearch window with all 16 retroviral protein sequences pasted into the text box.
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        •   Figure Figure 14.4.27 A 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.
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        Videos

        Literature Cited

           Bairoch, A., Apweiler. R., Wu, C.H., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M.J., Natale, D.A., O'Donovan, C., Redaschi, N., and Yeh, L.S. 2005. The Universal Protein Resource (UniProt). Nucl. Acids Res. 33:D154‐D159.
           Bateman, A., Coin, L., Durbin, R., Finn, R.D., Hollich, V., Griffiths‐Jones, S., Khanna, A., Marshall, M., Moxon, S., Sonnhammer, E.L., Studholme, D.J., Yeats, C., and Eddy, S.R. 2004. The Pfam protein families database. Nucl. Acids Res. 32:D138‐D141.
           Brooksbank, C., Cameron, G., and Thornton, J. 2005. The European Bioinformatics Institute's data resources: Towards systems biology. Nucl. Acids Res. 33:D46‐D53.
           Chen, X., Ji, Z.L., and Chen, Y.Z. 2002. TTD: Therapeutic Target Database. Nucl. Acids Res. 30:412‐415.
           Halgren, T.A., Murphy, R.B., Friesner, R.A., Beard, H.S., Frye, L.L., Pollard, W.T., and Banks, J.L. 2004. Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem. 47:1750‐1709.
           Hatfield, C.L., May, S.K., and Markoff, J.S. 1999. Quality of consumer drug information provided by four Web sites. Am. J. Health Syst. Pharm. 56:2308‐2311.
           Hewett, M., Oliver, D.E., Rubin, D.L., Easton, K.L., Stuart, J.M., Altman, R.B., and Klein, T.E. 2002. PharmGKB: The Pharmacogenetics Knowledge Base. Nucl. Acids Res. 30:163‐165.
           Hulo, N., Sigrist, C.J., Le Saux, V., Langendijk‐Genevaux, P.S., Bordoli, L., Gattiker, A., De Castro, E., Bucher, P., and Bairoch, A. 2004. Recent improvements to the PROSITE database. Nucl. Acids Res. 32:D134‐D137.
           Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y., and Hattori, M. 2004. The KEGG resource for deciphering the genome. Nucl. Acids Res. 32:D277‐D280.
           Kramer, B., Rarey, M., and Lengauer, T. 1997. CASP2 experiences with docking flexible ligands using FlexX. Proteins 1:221‐225.
           Krogh, A., Larsson, B., von Heijne, G., and Sonnhammer, E.L. 2001. Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes. J. Mol. Biol. 305:567‐580.
           Manber, U. and Bigot, P. 1997. USENIX Symposium on Internet Technologies and Systems (NSITS'97), Monterey, Calif., pp. 231‐239.
           McGuffin, L.J., Bryson, K., and Jones, D.T. 2000. The PSIPRED protein structure prediction server. Bioinformatics 16:404‐405.
           Montgomerie, S., Sundararaj, S., Gallin, W.J., and Wishart, D.S. 2006. Improving the accuracy of protein secondary structure prediction using structural alignment. BMC Bioinformatics 7:301‐312.
           Orth, A.P., Batalov, S., Perrone, M., and Chanda, S.K. 2004. The promise of genomics to identify novel therapeutic targets. Expert Opin. Ther. Targets 8:587‐596.
           Rebhan, M., Chalifa‐Caspi, V., Prilusky, J., and Lancet, D. 1998. GeneCards: A novel functional genomics compendium with automated data mining and query reformulation support. Bioinformatics 14:656‐664.
           Sadowski, J. and Gasteiger, J. 1993. From atoms to bonds to three‐dimensional atomic coordinates: Automatic model builders. Chem. Rev. 93:2567‐2581.
           Weininger, D. 1988. SMILES 1. Introduction and encoding rules. J. Chem. Inf. Comput. Sci. 28:31‐38.
           Wheeler, D.L., Barrett, T., Benson, D.A., Bryant, S.H., Canese, K., Church, D.M., DiCuccio, M., Edgar, R., Federhen, S., Helmberg, W., Kenton, D.L., Khovayko, O., Lipman, D.J., Madden, T.L., Maglott, D.R., Ostell, J., Pontius, J.U., Pruitt, K.D., Schuler, G.D., Schriml, L.M., Sequeira, E., Sherry, S.T., Sirotkin, K., Starchenko, G., Suzek, T.O., Tatusov, R., Tatusova, T.A., Wagner, L., and Yaschenko, E. 2005. Database resources of the National Center for Biotechnology Information. Nucl. Acids Res. 33:D39‐D45.
           Willard, L., Ranjan, A., Zhang, H., Monzavi, H., Boyko, R.F., Sykes, B.D., and Wishart, D.S. 2003. VADAR: A web server for quantitative evaluation of protein structure quality. Nucl. Acids Res. 31:3316‐3319.
           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.
           Zhang, R., Ou, H.Y., and Zhang, C.T. 2004. DEG, a Database of Essential Genes. Nucl. Acids Res. 32:D271‐D272
        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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        PDF or HTML at Wiley Online Library
         
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