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Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis

Drug and fragment screening at X-ray crystallography beamlines has been a huge success. However, it is inevitable that more high-profile biological drug targets will be identified for which high-quality, highly homogenous crystal systems cannot be found. With increasing heterogeneity in crystal syst...

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Autor principal: Ginn, Helen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604910/
https://www.ncbi.nlm.nih.gov/pubmed/33135684
http://dx.doi.org/10.1107/S2059798320012619
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author Ginn, Helen M.
author_facet Ginn, Helen M.
author_sort Ginn, Helen M.
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description Drug and fragment screening at X-ray crystallography beamlines has been a huge success. However, it is inevitable that more high-profile biological drug targets will be identified for which high-quality, highly homogenous crystal systems cannot be found. With increasing heterogeneity in crystal systems, the application of current multi-data-set methods becomes ever less sensitive to bound ligands. In order to ease the bottleneck of finding a well behaved crystal system, pre-clustering of data sets can be carried out using cluster4x after data collection to separate data sets into smaller partitions in order to restore the sensitivity of multi-data-set methods. Here, the software cluster4x is introduced for this purpose and validated against published data sets using PanDDA, showing an improved total signal from existing ligands and identifying new hits in both highly heterogenous and less heterogenous multi-data sets. cluster4x provides the researcher with an interactive graphical user interface with which to explore multi-data set experiments.
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spelling pubmed-76049102020-11-17 Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis Ginn, Helen M. Acta Crystallogr D Struct Biol Research Papers Drug and fragment screening at X-ray crystallography beamlines has been a huge success. However, it is inevitable that more high-profile biological drug targets will be identified for which high-quality, highly homogenous crystal systems cannot be found. With increasing heterogeneity in crystal systems, the application of current multi-data-set methods becomes ever less sensitive to bound ligands. In order to ease the bottleneck of finding a well behaved crystal system, pre-clustering of data sets can be carried out using cluster4x after data collection to separate data sets into smaller partitions in order to restore the sensitivity of multi-data-set methods. Here, the software cluster4x is introduced for this purpose and validated against published data sets using PanDDA, showing an improved total signal from existing ligands and identifying new hits in both highly heterogenous and less heterogenous multi-data sets. cluster4x provides the researcher with an interactive graphical user interface with which to explore multi-data set experiments. International Union of Crystallography 2020-10-16 /pmc/articles/PMC7604910/ /pubmed/33135684 http://dx.doi.org/10.1107/S2059798320012619 Text en © Ginn 2020 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Papers
Ginn, Helen M.
Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis
title Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis
title_full Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis
title_fullStr Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis
title_full_unstemmed Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis
title_short Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis
title_sort pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604910/
https://www.ncbi.nlm.nih.gov/pubmed/33135684
http://dx.doi.org/10.1107/S2059798320012619
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