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Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking
[Image: see text] A key metric to assess molecular docking remains ligand enrichment against challenging decoys. Whereas the directory of useful decoys (DUD) has been widely used, clear areas for optimization have emerged. Here we describe an improved benchmarking set that includes more diverse targ...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405771/ https://www.ncbi.nlm.nih.gov/pubmed/22716043 http://dx.doi.org/10.1021/jm300687e |
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author | Mysinger, Michael M. Carchia, Michael Irwin, John. J. Shoichet, Brian K. |
author_facet | Mysinger, Michael M. Carchia, Michael Irwin, John. J. Shoichet, Brian K. |
author_sort | Mysinger, Michael M. |
collection | PubMed |
description | [Image: see text] A key metric to assess molecular docking remains ligand enrichment against challenging decoys. Whereas the directory of useful decoys (DUD) has been widely used, clear areas for optimization have emerged. Here we describe an improved benchmarking set that includes more diverse targets such as GPCRs and ion channels, totaling 102 proteins with 22886 clustered ligands drawn from ChEMBL, each with 50 property-matched decoys drawn from ZINC. To ensure chemotype diversity, we cluster each target’s ligands by their Bemis–Murcko atomic frameworks. We add net charge to the matched physicochemical properties and include only the most dissimilar decoys, by topology, from the ligands. An online automated tool (http://decoys.docking.org) generates these improved matched decoys for user-supplied ligands. We test this data set by docking all 102 targets, using the results to improve the balance between ligand desolvation and electrostatics in DOCK 3.6. The complete DUD-E benchmarking set is freely available at http://dude.docking.org. |
format | Online Article Text |
id | pubmed-3405771 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-34057712012-07-26 Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking Mysinger, Michael M. Carchia, Michael Irwin, John. J. Shoichet, Brian K. J Med Chem [Image: see text] A key metric to assess molecular docking remains ligand enrichment against challenging decoys. Whereas the directory of useful decoys (DUD) has been widely used, clear areas for optimization have emerged. Here we describe an improved benchmarking set that includes more diverse targets such as GPCRs and ion channels, totaling 102 proteins with 22886 clustered ligands drawn from ChEMBL, each with 50 property-matched decoys drawn from ZINC. To ensure chemotype diversity, we cluster each target’s ligands by their Bemis–Murcko atomic frameworks. We add net charge to the matched physicochemical properties and include only the most dissimilar decoys, by topology, from the ligands. An online automated tool (http://decoys.docking.org) generates these improved matched decoys for user-supplied ligands. We test this data set by docking all 102 targets, using the results to improve the balance between ligand desolvation and electrostatics in DOCK 3.6. The complete DUD-E benchmarking set is freely available at http://dude.docking.org. American Chemical Society 2012-06-20 2012-07-26 /pmc/articles/PMC3405771/ /pubmed/22716043 http://dx.doi.org/10.1021/jm300687e Text en Copyright © 2012 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. |
spellingShingle | Mysinger, Michael M. Carchia, Michael Irwin, John. J. Shoichet, Brian K. Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking |
title | Directory of Useful Decoys,
Enhanced (DUD-E): Better
Ligands and Decoys for Better Benchmarking |
title_full | Directory of Useful Decoys,
Enhanced (DUD-E): Better
Ligands and Decoys for Better Benchmarking |
title_fullStr | Directory of Useful Decoys,
Enhanced (DUD-E): Better
Ligands and Decoys for Better Benchmarking |
title_full_unstemmed | Directory of Useful Decoys,
Enhanced (DUD-E): Better
Ligands and Decoys for Better Benchmarking |
title_short | Directory of Useful Decoys,
Enhanced (DUD-E): Better
Ligands and Decoys for Better Benchmarking |
title_sort | directory of useful decoys,
enhanced (dud-e): better
ligands and decoys for better benchmarking |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405771/ https://www.ncbi.nlm.nih.gov/pubmed/22716043 http://dx.doi.org/10.1021/jm300687e |
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