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Is it possible to i...
Is it possible to increase hit rates in structure-based virtual screening by pharmacophore filtering? : An investigation of the advantages and pitfalls of post-filtering
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- Muthas, Daniel (författare)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Sabnis, Yogesh A (författare)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Lundborg, Magnus (författare)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Karlén, Anders (författare)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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(creator_code:org_t)
- Elsevier BV, 2008
- 2008
- Engelska.
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Ingår i: Journal of Molecular Graphics and Modelling. - : Elsevier BV. - 1093-3263 .- 1873-4243. ; 26:8, s. 1237-1251
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- We have investigated the influence of post-filtering virtual screening results, with pharmacophoric features generated from an X-ray structure, on enrichment rates. This was performed using three docking softwares, zdock+, Surflex and FRED, as virtual screening tools and pharmacophores generated in UNITY from co-crystallized complexes. Sets of known actives along with 9997 pharmaceutically relevant decoy compounds were docked against six chemically diverse protein targets namely CDK2, COX2, ERalpha, fXa, MMP3, and NA. To try to overcome the inherent limitations of the well-known docking problem, we generated multiple poses for each compound. The compounds were first ranked according to their scores alone and enrichment rates were calculated using only the top scoring pose of each compound. Subsequently, all poses for each compound were passed through the different pharmacophores generated from co-crystallized complexes and the enrichment factors were re-calculated based on the top-scoring passing pose of each compound. Post-filtering with a pharmacophore generated from only one X-ray complex was shown to increase enrichment rates in all investigated targets compared to docking alone. This indicates that this is a general method, which works for diverse targets and different docking softwares.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Flo(+)
- surflex
- FRED
- enrichment factor
- docking performance
- structure-based virtual screening
- pharmacophore filtering
- PHARMACY
- FARMACI
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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