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. 2009 Jul 30:8:178.
doi: 10.1186/1475-2875-8-178.

Discovery: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria

Fourie Joubert  1 , Claudia M Harrison, Riaan J Koegelenberg, Christiaan J Odendaal, Tjaart A P de Beer
Affiliations

Discovery: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria

Fourie Joubert et al. Malar J. .

Abstract

Background: Up to half a billion human clinical cases of malaria are reported each year, resulting in about 2.7 million deaths, most of which occur in sub-Saharan Africa. Due to the over-and misuse of anti-malarials, widespread resistance to all the known drugs is increasing at an alarming rate. Rational methods to select new drug target proteins and lead compounds are urgently needed. The Discovery system provides data mining functionality on extensive annotations of five malaria species together with the human and mosquito hosts, enabling the selection of new targets based on multiple protein and ligand properties.

Methods: A web-based system was developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein features used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions and host-pathogen interactions among others. Searching by chemical structure is also available.

Results: An in silico system for the selection of putative drug targets and lead compounds is presented, together with an example study on the bifunctional DHFR-TS from Plasmodium falciparum.

Conclusion: The Discovery system allows for the identification of putative drug targets and lead compounds in Plasmodium species based on the filtering of protein and chemical properties.

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Figures

Figure 1
Figure 1
A represenation of the major protein features displayed in the Discovery system, together with the sources of information.
Figure 2
Figure 2
The main Discovery interface, allowing ID, keyword, advanced protein property and chemical structure searches.
Figure 3
Figure 3
The Discovery summary page, showing the tabbed environment for the different result classes.
Figure 4
Figure 4
The Discovery results page for a chemical search, showing the compound properties and protein interaction tab.
Figure 5
Figure 5
A representation of the different types of searches available in the Discovery system.
See this image and copyright information in PMC

References

    1. Bjorkman A, Bhattarai A. Public health impact of drug resistant Plasmodium falciparum malaria. Acta Trop. 2005;94:163–169. - PubMed
    1. Dyer MD, Murali TM, Sobral BW. Computational prediction of host-pathogen protein-protein interactions. Bioinformatics. 2007;23:i159–166. doi: 10.1093/bioinformatics/btm208. - DOI - PubMed
    1. Doolittle RF. The grand assault. Nature. 2002;419:493–494. doi: 10.1038/419493a. - DOI - PubMed
    1. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002;419:498–511. doi: 10.1038/nature01097. - DOI - PMC - PubMed
    1. Birkholtz LM, Bastien O, Wells G, Grando D, Joubert F, Kasam V, Zimmermann M, Ortet P, Jacq N, Saidani N, Roy S, Hofmann-Apitius M, Breton V, Louw AI, Marechal E. Integration and mining of malaria molecular, functional and pharmacological data: how far are we from a chemogenomic knowledge space? Malar J. 2006;5:110–133. doi: 10.1186/1475-2875-5-110. - DOI - PMC - PubMed

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