TY - JOUR
T1 - A teach-discover-treat application of ZincPharmer
T2 - An online interactive pharmacophore modeling and virtual screening tool
AU - Koes, David Ryan
AU - Pabon, Nicolas A.
AU - Deng, Xiaoyi
AU - Phillips, Margaret A.
AU - Camacho, Carlos J.
N1 - Publisher Copyright:
© 2015 Koes et al.
PY - 2015/8/10
Y1 - 2015/8/10
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0134697
DO - 10.1371/journal.pone.0134697
M3 - Article
C2 - 26258606
AN - SCOPUS:84942474508
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 8
M1 - e0134697
ER -