A teach-discover-treat application of ZincPharmer: An online interactive pharmacophore modeling and virtual screening tool

David Ryan Koes, Nicolas A. Pabon, Xiaoyi Deng, Margaret A. Phillips, Carlos J. Camacho

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The 2012 Teach-Discover-Treat (TDT) community-wide experiment provided a unique opportunity to test prospective virtual screening protocols targeting the anti-malarial target dihydroorotate dehydrogenase (DHODH). Facilitated by ZincPharmer, an open access online interactive pharmacophore search of the ZINC database, the experience resulted in the development of a novel classification scheme that successfully predicted the bound structure of a non-triazolopyrimidine inhibitor, as well as an overall hit rate of 27% of tested active compounds from multiple novel chemical scaffolds. The general approach entailed exhaustively building and screening sparse pharmacophore models comprising of a minimum of three features for each bound ligand in all available DHODH co-crystals and iteratively adding features that increased the number of known binders returned by the query. Collectively, the TDT experiment provided a unique opportunity to teach computational methods of drug discovery, develop innovative methodologies and prospectively discover new compounds active against DHODH.

Original languageEnglish (US)
Article numbere0134697
JournalPLoS One
Volume10
Issue number8
DOIs
StatePublished - Aug 10 2015

Fingerprint

Screening
screening
antimalarials
crystals
Antimalarials
Drug Discovery
Computational methods
Scaffolds
drugs
Binders
Experiments
methodology
Databases
Ligands
Crystals
testing
dihydroorotate dehydrogenase
ligands

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A teach-discover-treat application of ZincPharmer : An online interactive pharmacophore modeling and virtual screening tool. / Koes, David Ryan; Pabon, Nicolas A.; Deng, Xiaoyi; Phillips, Margaret A.; Camacho, Carlos J.

In: PLoS One, Vol. 10, No. 8, e0134697, 10.08.2015.

Research output: Contribution to journalArticle

Koes, David Ryan ; Pabon, Nicolas A. ; Deng, Xiaoyi ; Phillips, Margaret A. ; Camacho, Carlos J. / A teach-discover-treat application of ZincPharmer : An online interactive pharmacophore modeling and virtual screening tool. In: PLoS One. 2015 ; Vol. 10, No. 8.
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