caa a22 4500 467938768 CHVBK 20180406153005.0 cr unu---uuuuu 170328e20061201xx s 000 0 eng 10.1007/s10822-006-9070-2 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9070-2 A marriage made in torsional space: using GALAHAD models to drive pharmacophore multiplet searches [Elektronische Daten] [Jennifer Shepphird, Robert Clark] Pharmacophore multiplets are useful tools for 3D database searching, with the queries used ordinarily being derived from ensembles of random conformations of active ligands. It seems reasonable to expect that their usefulness can be augmented by instead using queries derived from single ligand conformations obtained from aligned ligands. Comparisons of pharmacophore multiplet searching using random conformations with multiplet searching using single conformations derived from GALAHAD (a genetic algorithm with linear assignment for hypermolecular alignment of datasets) models do indeed show that, while query hypotheses based on random conformations are quite effective, hypotheses based on aligned conformations do a better job of discriminating between active and inactive compounds. In particular, the hypothesis created from a neuraminidase inhibitor model was more similar to half of 18 known actives than all but 0.2% of the compounds in a structurally diverse subset of the World Drug Index. Similarly, a model developed from five angiotensin II antagonists yielded hypotheses that placed 65 known antagonists within the top 0.1-1% of decoy databases. The differences in discriminating power ranged from 2 to 20-fold, depending on the protein target and the type of pharmacophore multiplet used. Springer Science+Business Media, LLC, 2006 GALAHAD nationallicence Molecular alignment nationallicence Pharmacophore nationallicence Pharmacophore multiplets nationallicence Tuplets nationallicence Virtual screening nationallicence ATII : Angiotensin II nationallicence CHDPA : Chapman and Hall Dictionary of Pharmaceutical Agents nationallicence GA : Genetic algorithm nationallicence GALAHAD : Genetic automated molecular overlays nationallicence ROC : Receiver Operating Characteristic nationallicence WDI : World Drug Index nationallicence Shepphird Jennifer Informatics Research Center, Tripos Inc., 1699 South Hanley Road, 63144, St. Louis, MO, USA aut Clark Robert Informatics Research Center, Tripos Inc., 1699 South Hanley Road, 63144, St. Louis, MO, USA aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/12(2006-12-01), 763-771 0920-654X 20:12<763 2006 20 10822 https://doi.org/10.1007/s10822-006-9070-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9070-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shepphird Jennifer Informatics Research Center, Tripos Inc., 1699 South Hanley Road, 63144, St. Louis, MO, USA aut NATIONALLICENCE 700 1- Clark Robert Informatics Research Center, Tripos Inc., 1699 South Hanley Road, 63144, St. Louis, MO, USA aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/12(2006-12-01), 763-771 0920-654X 20:12<763 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer