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

Joubert F, Harrison CM, Koegelenberg RJ, Odendaal CJ, de Beer TA - Malar. J. (2009)

Bottom Line: Searching by chemical structure is also available.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics and Computational Biology Unit, Department of Biochemistry, University of Pretoria, Pretoria, South Africa. fourie.joubert@up.ac.za

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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Related in: MedlinePlus

A representation of the different types of searches available in the Discovery system.
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Figure 5: A representation of the different types of searches available in the Discovery system.

Mentions: When approaching the search from the ligand perspective, the user may search by ligand keyword, or by drawing a chemical structure using the Marvin applet. Different methods are then available to search with the structure against ligands from KEGG, PDB and DrugBank using the ChemAxon JChem Base functionality. Results are displayed as a JChem table, and the user may select a compound to view further information. A view is then provided of the compound's structure, ADMET properties as pre-calculated in JChem Base and possible interacting proteins based on KEGG annotations, and BLAST results against PDB and DrugBank (Figure 4). The query processes followed for the different types of searches described above are summarized in Figure 5.


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

Joubert F, Harrison CM, Koegelenberg RJ, Odendaal CJ, de Beer TA - Malar. J. (2009)

A representation of the different types of searches available in the Discovery system.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724543&req=5

Figure 5: A representation of the different types of searches available in the Discovery system.
Mentions: When approaching the search from the ligand perspective, the user may search by ligand keyword, or by drawing a chemical structure using the Marvin applet. Different methods are then available to search with the structure against ligands from KEGG, PDB and DrugBank using the ChemAxon JChem Base functionality. Results are displayed as a JChem table, and the user may select a compound to view further information. A view is then provided of the compound's structure, ADMET properties as pre-calculated in JChem Base and possible interacting proteins based on KEGG annotations, and BLAST results against PDB and DrugBank (Figure 4). The query processes followed for the different types of searches described above are summarized in Figure 5.

Bottom Line: Searching by chemical structure is also available.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics and Computational Biology Unit, Department of Biochemistry, University of Pretoria, Pretoria, South Africa. fourie.joubert@up.ac.za

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.

Show MeSH
Related in: MedlinePlus