title: Discovery-2: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria.
abstract: BACKGROUND
  Drug resistance to anti-malarial compounds remains a serious problem, with resistance to newer pharmaceuticals developing at an alarming rate. The development of new anti-malarials remains a priority, and the rational selection of putative targets is a key element of this process. Discovery-2 is an update of the original Discovery in silico resource for the rational selection of putative drug target proteins, enabling researchers to obtain information for a protein which may be useful for the selection of putative drug targets, and to perform advanced filtering of proteins encoded by the malaria genome based on a series of molecular properties.
  
  
  METHODS
  An updated in silico resource has been 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 properties used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions. Newly added features include drugability measures from ChEMBL, automated literature relations and links to clinical trial information. Searching by chemical structure is also available.
  
  
  RESULTS
  The updated functionality of the Discovery-2 resource is presented, together with a detailed case study of the Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase (PfSAHH) protein. A short example of a chemical search with pyrimethamine is also illustrated.
  
  
  CONCLUSIONS
  The updated Discovery-2 resource allows researchers to obtain detailed properties of proteins from the malaria genome, which may be of interest in the target selection process, and to perform advanced filtering and selection of proteins based on a relevant range of molecular characteristics.
authors.affiliation: Bioinformatics and Computational Biology Unit, Department of Biochemistry, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Phelelani T
authors.initials: PT
authors.lastname: Mpangase
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Szolkiewicz
authors.forename: Misha
authors.initials: M
authors.lastname: le Grange
authors.forename: Jeanré H
authors.initials: JH
authors.lastname: Smit
authors.forename: Pieter B
authors.initials: PB
authors.lastname: Burger
authors.forename: Fourie
authors.initials: F
authors.lastname: Joubert
mesh_terms: D000962:Antimalarials / Q000302:isolation & purification*; D019295:Computational Biology / Q000379:methods*; D057225:Data Mining / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000962:Antimalarials
references.citation: Bioinformatics. 2009 Jan 15;25(2):288-9
references.pmid: 19033274
references.citation: PLoS Negl Trop Dis. 2009;3(4):e418
references.pmid: 19381286
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D565-70
references.pmid: 22123736
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D670-6
references.pmid: 21062828
references.citation: Trends Parasitol. 2011 Jul;27(7):285-6
references.pmid: 21493145
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D109-14
references.pmid: 22080510
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D539-43
references.pmid: 18957442
references.citation: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references.pmid: 11259830
references.citation: Curr Opin Infect Dis. 2011 Dec;24(6):570-7
references.pmid: 22001944
references.citation: Curr Protoc Bioinformatics. 2011 Sep;Chapter 6:Unit 6.12.1-19
references.pmid: 21901743
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D465-74
references.pmid: 21097780
references.citation: PLoS Biol. 2003 Oct;1(1):E5
references.pmid: 12929205
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D306-12
references.pmid: 22096229
references.citation: J Med Chem. 2002 Jan 31;45(3):748-51
references.pmid: 11806727
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):304-5
references.pmid: 10592255
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D691-7
references.pmid: 21067998
references.citation: N Engl J Med. 2009 Jul 30;361(5):455-67
references.pmid: 19641202
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D729-34
references.pmid: 22135296
references.citation: Genome Res. 2006 Apr;16(4):542-9
references.pmid: 16520460
references.citation: Mol Biosyst. 2012 Jun;8(6):1678-85
references.pmid: 22446744
references.citation: Database (Oxford). 2011 Mar 29;2011:bar009
references.pmid: 21447597
references.citation: Malar J. 2009 Jul 30;8:178
references.pmid: 19642978
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D367-72
references.pmid: 20935044
references.citation: J Biol Chem. 1994 Jun 10;269(23):16364-70
references.pmid: 8206944
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D84-90
references.pmid: 22086963
references.citation: Nat Rev Drug Discov. 2008 Nov;7(11):900-7
references.pmid: 18927591