A Teach-Discover-Treat Application of ZincPharmer: An Online Interactive Pharmacophore Modeling and Virtual Screening Tool.
Where this comes from
- Record sourced from PubMed, PMID 26258606.
- Also identified by DOI 10.1371/journal.pone.0134697 and PMC identifier 4530941.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Antimalarials
- Drug Design
- Molecular Docking Simulation