Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

Hdl Handle:
http://hdl.handle.net/10147/94171
Title:
Genomes2Drugs: identifies target proteins and lead drugs from proteome data.
Authors:
Toomey, David; Hoppe, Heinrich C; Brennan, Marian P; Nolan, Kevin B; Chubb, Anthony J
Affiliation:
Molecular Modelling Group, Royal College of Surgeons in Ireland, Dublin, Ireland.
Citation:
Genomes2Drugs: identifies target proteins and lead drugs from proteome data. 2009, 4 (7):e6195 PLoS ONE
Journal:
PloS one
Issue Date:
2009
URI:
http://hdl.handle.net/10147/94171
DOI:
10.1371/journal.pone.0006195
PubMed ID:
19593435
Abstract:
BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under 'change-of-application' patents.
Language:
en
MeSH:
Animals; Antimalarials; Drug Discovery; Genome, Protozoan; Humans; Plasmodium falciparum; Proteome
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorToomey, Daviden
dc.contributor.authorHoppe, Heinrich Cen
dc.contributor.authorBrennan, Marian Pen
dc.contributor.authorNolan, Kevin Ben
dc.contributor.authorChubb, Anthony Jen
dc.date.accessioned2010-03-12T15:37:01Z-
dc.date.available2010-03-12T15:37:01Z-
dc.date.issued2009-
dc.identifier.citationGenomes2Drugs: identifies target proteins and lead drugs from proteome data. 2009, 4 (7):e6195 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid19593435-
dc.identifier.doi10.1371/journal.pone.0006195-
dc.identifier.urihttp://hdl.handle.net/10147/94171-
dc.description.abstractBACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under 'change-of-application' patents.-
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshAntimalarials-
dc.subject.meshDrug Discovery-
dc.subject.meshGenome, Protozoan-
dc.subject.meshHumans-
dc.subject.meshPlasmodium falciparum-
dc.subject.meshProteome-
dc.titleGenomes2Drugs: identifies target proteins and lead drugs from proteome data.en
dc.contributor.departmentMolecular Modelling Group, Royal College of Surgeons in Ireland, Dublin, Ireland.en
dc.identifier.journalPloS oneen

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