{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T08:45:18Z","timestamp":1725439518049},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T00:00:00Z","timestamp":1564185600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012681","name":"CNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012681","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008222","name":"University of Montpellier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008222","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"EU Horizon 2020","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"crossref"}]},{"name":"GOLIATH","award":["825489"]},{"DOI":"10.13039\/501100007546","name":"ANSES","doi-asserted-by":"publisher","award":["EST-2016\/1\/162-XENomix"],"id":[{"id":"10.13039\/501100007546","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"Abstract<\/jats:title>\n \n Motivation<\/jats:title>\n Nowadays, virtual screening (VS) plays a major role in the process of drug development. Nonetheless, an accurate estimation of binding affinities, which is crucial at all stages, is not trivial and may require target-specific fine-tuning. Furthermore, drug design also requires improved predictions for putative secondary targets among which is Estrogen Receptor alpha (ER\u03b1).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n VS based on combinations of Structure-Based VS (SBVS) and Ligand-Based VS (LBVS) is gaining momentum to improve VS performances. In this study, we propose an integrated approach using ligand docking on multiple structural ensembles to reflect receptor flexibility. Then, we investigate the impact of the two different types of features (structure-based and ligand molecular descriptors) on affinity predictions using a random forest algorithm. We find that ligand-based features have lower predictive power (rP = 0.69, R2 = 0.47) than structure-based features (rP = 0.78, R2 = 0.60). Their combination maintains high accuracy (rP = 0.73, R2 = 0.50) on the internal test set, but it shows superior robustness on external datasets. Further improvement and extending the training dataset to include xenobiotics, leads to a novel high-throughput affinity prediction method for ER\u03b1 ligands (rP = 0.85, R2 = 0.71). The presented prediction tool is provided to the community as a dedicated satellite of the @TOME server in which one can upload a ligand dataset in mol2 format and get ligand docked and affinity predicted.<\/jats:p>\n <\/jats:sec>\n \n Availability and implementation<\/jats:title>\n http:\/\/edmon.cbs.cnrs.fr.<\/jats:p>\n <\/jats:sec>\n \n Supplementary information<\/jats:title>\n Supplementary data are available at Bioinformatics online.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz538","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T11:27:00Z","timestamp":1563967620000},"page":"160-168","source":"Crossref","is-referenced-by-count":19,"title":["Towards accurate high-throughput ligand affinity prediction by exploiting structural ensembles, docking metrics and ligand similarity"],"prefix":"10.1093","volume":"36","author":[{"given":"Melanie","family":"Schneider","sequence":"first","affiliation":[{"name":"Centre de Biochimie Structurale, CNRS, INSERM, Univ Montpellier , 34090 Montpellier, France"}]},{"given":"Jean-Luc","family":"Pons","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, CNRS, INSERM, Univ Montpellier , 34090 Montpellier, France"}]},{"given":"William","family":"Bourguet","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, CNRS, INSERM, Univ Montpellier , 34090 Montpellier, France"}]},{"given":"Gilles","family":"Labesse","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, CNRS, INSERM, Univ Montpellier , 34090 Montpellier, France"}]}],"member":"286","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"2023013109501510800_btz538-B1","doi-asserted-by":"crossref","first-page":"6724","DOI":"10.1021\/es049665h","article-title":"Consensus kNN QSAR: a versatile method for predicting the estrogenic activity of organic compounds in silico. 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