Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria

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dc.contributor.advisor Joubert, Fourie en
dc.contributor.postgraduate Mpangase, Phelelani Thokozani en
dc.date.accessioned 2013-09-06T18:11:34Z
dc.date.available 2013-05-24 en
dc.date.available 2013-09-06T18:11:34Z
dc.date.created 2013-04-12 en
dc.date.issued 2012 en
dc.date.submitted 2013-05-15 en
dc.description Dissertation (MSc)--University of Pretoria, 2012. en
dc.description.abstract Current anti-malarial methods have been effective in reducing the number of malarial cases. However, these methods do not completely block the transmission of the parasite. Research has shown that repeated use of the current anti-malarial drugs, which include artemisinin-based drug combinations, might be toxic to humans. There have also been reports of an emergence of artemisinin-resistant parasites. Finding anti-malarial drugs through the drug discovery process takes a long time and failure results in a great financial loss. The failure of drug discovery projects can be partly attributed to the improper selection of drug targets. There is thus a need for an eff ective way of identifying and validating new potential malaria drug targets for entry into the drug discovery process. The availability of the genome sequences for the Plasmodium parasite, human host and the Anopheles mosquito vector has facilitated post-genomic studies on malaria. Proper utilizationof this data, in combination with computational biology and bioinformatics techniques, could aid in the in silico prioritization of drug targets. This study was aimed at extensively annotating the protein sequences from the Plasmodium parasites, H. sapiens and A. gambiae with data from di fferent online databases in order to create a resource for the prioritization of drug targets in malaria. Essentiality, assay feasibility, resistance, toxicity, structural information and druggability were the main target selection criteria which were used to collect data for protein annotations. The data was used to populate the Discovery resource (http://malport. bi.up.ac.za/) for the in silico prioritization of potential drug targets. A new version of the Discovery system, Discovery 2.0 (http://discovery.bi.up.ac.za/), has been developed using Java. The system contains new and automatically updated data as well as improved functionalities. The new data in Discovery 2.0 includes UniProt accessions, gene ontology annotations from the UniProt-GOA project, pathways from Reactome and Malaria Parasite Metabolic Pathways databases, protein-protein interactions data from. IntAct as well as druggability data from the DrugEBIlity resource hosted by ChEMBL. Users can access the data by searching with a protein identi er, UniProt accession, protein name or through the advanced search which lets users filter protein sequences based on different protein properties. The results are organized in a tabbed environment, with each tab displaying different protein annotation data. A sample investigation using a previously proposed malarial target, S-adenosyl-Lhomocysteine hydrolase, was carried out to demonstrate the diff erent categories of data available in Discovery 2.0 as well as to test if the available data is su fficient for assessment and prioritization of drug targets. The study showed that using the annotation data in Discovery 2.0, a protein can be assessed, in a species comparative manner, on the potential of being a drug target based on the selection criteria mentioned here. However, supporting data from literature is also needed to further validate the findings. en
dc.description.availability unrestricted en
dc.description.department Biochemistry en
dc.identifier.citation Mpangase, PT 2012, Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria, MSc dissertation, University of Pretoria, Pretoria, viewed yymmdd < http://hdl.handle.net/2263/24715 > en
dc.identifier.other E13/4/463/gm en
dc.identifier.upetdurl http://upetd.up.ac.za/thesis/available/etd-05152013-120636/ en
dc.identifier.uri http://hdl.handle.net/2263/24715
dc.language.iso en
dc.publisher University of Pretoria en_ZA
dc.rights © 2012 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria en
dc.subject Anti-malarial drugs en
dc.subject Plasmodium parasites en
dc.subject H. sapiens en
dc.subject A. gambiae en
dc.subject Protein sequences en
dc.subject UCTD en_US
dc.title Integrating protein annotations for the in silico prioritization of putative drug target proteins in malaria en
dc.type Dissertation en


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