{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T15:00:26Z","timestamp":1776092426173,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"7805","license":[{"start":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T00:00:00Z","timestamp":1583712000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T00:00:00Z","timestamp":1583712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2020,4,30]]},"DOI":"10.1038\/s41586-020-2117-z","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T13:03:07Z","timestamp":1583758987000},"page":"663-668","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":531,"title":["An open-source drug discovery platform enables ultra-large virtual screens"],"prefix":"10.1038","volume":"580","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6986-5270","authenticated-orcid":false,"given":"Christoph","family":"Gorgulla","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9810-7241","authenticated-orcid":false,"given":"Andras","family":"Boeszoermenyi","sequence":"additional","affiliation":[]},{"given":"Zi-Fu","family":"Wang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4160-5295","authenticated-orcid":false,"given":"Patrick D.","family":"Fischer","sequence":"additional","affiliation":[]},{"given":"Paul W.","family":"Coote","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-4256","authenticated-orcid":false,"given":"Krishna M.","family":"Padmanabha Das","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3029-3065","authenticated-orcid":false,"given":"Yehor S.","family":"Malets","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5444-7754","authenticated-orcid":false,"given":"Dmytro S.","family":"Radchenko","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6073-002X","authenticated-orcid":false,"given":"Yurii S.","family":"Moroz","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-528X","authenticated-orcid":false,"given":"David A.","family":"Scott","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-3672","authenticated-orcid":false,"given":"Konstantin","family":"Fackeldey","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-8586","authenticated-orcid":false,"given":"Moritz","family":"Hoffmann","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9006-4010","authenticated-orcid":false,"given":"Iryna","family":"Iavniuk","sequence":"additional","affiliation":[]},{"given":"Gerhard","family":"Wagner","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7281-1289","authenticated-orcid":false,"given":"Haribabu","family":"Arthanari","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,3,9]]},"reference":[{"key":"2117_CR1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jhealeco.2016.01.012","volume":"47","author":"JA DiMasi","year":"2016","unstructured":"DiMasi, J. A., Grabowski, H. G. & Hansen, R. W. Innovation in the pharmaceutical industry: new estimates of R&D costs. J. Health Econ. 47, 20\u201333 (2016).","journal-title":"J. Health Econ."},{"key":"2117_CR2","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41586-019-0917-9","volume":"566","author":"J Lyu","year":"2019","unstructured":"Lyu, J. et al. Ultra-large library docking for discovering new chemotypes. Nature 566, 224\u2013229 (2019).","journal-title":"Nature"},{"key":"2117_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-126","volume":"9","author":"S Zhang","year":"2008","unstructured":"Zhang, S., Kumar, K., Jiang, X., Wallqvist, A. & Reifman, J. DOVIS: an implementation for high-throughput virtual screening using AutoDock. BMC Bioinformatics 9, 126 (2008).","journal-title":"BMC Bioinformatics"},{"key":"2117_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/1752-153X-2-18","volume":"2","author":"X Jiang","year":"2008","unstructured":"Jiang, X., Kumar, K., Hu, X., Wallqvist, A. & Reifman, J. DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0. Chem. Cent. J. 2, 18 (2008).","journal-title":"Chem. Cent. J."},{"key":"2117_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15571-7","volume":"7","author":"NM Hassan","year":"2017","unstructured":"Hassan, N. M., Alhossary, A. A., Mu, Y. & Kwoh, C.-K. Protein-ligand blind docking using QuickVina-W with inter-process spatio-temporal integration. Sci. Rep. 7, 15451 (2017).","journal-title":"Sci. Rep."},{"key":"2117_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.0.CO;2-6","volume":"16","author":"RS Bohacek","year":"1996","unstructured":"Bohacek, R. S., McMartin, C. & Guida, W. C. The art and practice of structure-based drug design: a molecular modeling perspective. Med. Res. Rev. 16, 3\u201350 (1996).","journal-title":"Med. Res. Rev."},{"key":"2117_CR7","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1124\/jpet.117.241794","volume":"363","author":"JG Yonchuk","year":"2017","unstructured":"Yonchuk, J. G. et al. Characterization of the potent, selective Nrf2 activator, 3-(pyridin-3-ylsulfonyl)-5-(trifluoromethyl)-2H-chromen-2-one, in cellular and in vivo models of pulmonary oxidative stress. J. Pharmacol. Exp. Ther. 363, 114\u2013125 (2017).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2117_CR8","doi-asserted-by":"publisher","first-page":"8088","DOI":"10.1021\/acs.jmedchem.8b00358","volume":"61","author":"JS Pallesen","year":"2018","unstructured":"Pallesen, J. S., Tran, K. T. & Bach, A. Non-covalent small-molecule Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Keap1\u2013Nrf2) inhibitors and their potential for targeting central nervous system diseases. J. Med. Chem. 61, 8088\u20138103 (2018).","journal-title":"J. Med. Chem."},{"key":"2117_CR9","doi-asserted-by":"publisher","first-page":"3991","DOI":"10.1021\/acs.jmedchem.6b00228","volume":"59","author":"TG Davies","year":"2016","unstructured":"Davies, T. G. et al. Monoacidic inhibitors of the Kelch-like ECH-associated protein 1: nuclear factor erythroid 2-related factor 2 (KEAP1:NRF2) protein\u2013protein interaction with high cell potency identified by fragment-based discovery. J. Med. Chem. 59, 3991\u20134006 (2016).","journal-title":"J. Med. Chem."},{"key":"2117_CR10","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","volume":"18","author":"A Cuadrado","year":"2019","unstructured":"Cuadrado, A. et al. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat. Rev. Drug Discov. 18, 295\u2013317 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"2117_CR11","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","volume":"55","author":"T Sterling","year":"2015","unstructured":"Sterling, T. & Irwin, J. J. ZINC 15\u2014ligand discovery for everyone. J. Chem. Inf. Model. 55, 2324\u20132337 (2015).","journal-title":"J. Chem. Inf. Model."},{"key":"2117_CR12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455\u2013461 (2010).","journal-title":"J. Comput. Chem."},{"key":"2117_CR13","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1093\/bioinformatics\/btv082","volume":"31","author":"A Alhossary","year":"2015","unstructured":"Alhossary, A., Handoko, S. D., Mu, Y. & Kwoh, C.-K. Fast, accurate, and reliable molecular docking with QuickVina 2. Bioinformatics 31, 2214\u20132216 (2015).","journal-title":"Bioinformatics"},{"key":"2117_CR14","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1021\/ci300604z","volume":"53","author":"DR Koes","year":"2013","unstructured":"Koes, D. R., Baumgartner, M. P. & Camacho, C. J. Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise. J. Chem. Inf. Model. 53, 1893\u20131904 (2013).","journal-title":"J. Chem. Inf. Model."},{"key":"2117_CR15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004586","volume":"11","author":"PA Ravindranath","year":"2015","unstructured":"Ravindranath, P. A., Forli, S., Goodsell, D. S., Olson, A. J. & Sanner, M. F. AutoDockFR: advances in protein-ligand docking with explicitly specified binding site flexibility. PLOS Comput. Biol. 11, e1004586 (2015).","journal-title":"PLOS Comput. Biol."},{"key":"2117_CR16","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13321-016-0139-1","volume":"8","author":"MR Koebel","year":"2016","unstructured":"Koebel, M. R., Schmadeke, G., Posner, R. G. & Sirimulla, S. AutoDock VinaXB: implementation of XBSF, new empirical halogen bond scoring function, into AutoDock Vina. J. Cheminform. 8, 27 (2016).","journal-title":"J. Cheminform."},{"key":"2117_CR17","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1021\/acs.jctc.5b00834","volume":"12","author":"AK Nivedha","year":"2016","unstructured":"Nivedha, A. K., Thieker, D. F., Makeneni, S., Hu, H. & Woods, R. J. Vina-Carb: improving glycosidic angles during carbohydrate docking. J. Chem. Theory Comput. 12, 892\u2013901 (2016).","journal-title":"J. Chem. Theory Comput."},{"key":"2117_CR18","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1016\/j.bpj.2018.02.038","volume":"114","author":"RE Amaro","year":"2018","unstructured":"Amaro, R. E. et al. Ensemble docking in drug discovery. Biophys. J. 114, 2271\u20132278 (2018).","journal-title":"Biophys. J."},{"key":"2117_CR19","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1021\/ci300399w","volume":"53","author":"DR Houston","year":"2013","unstructured":"Houston, D. R. & Walkinshaw, M. D. Consensus docking: improving the reliability of docking in a virtual screening context. J. Chem. Inf. Model. 53, 384\u2013390 (2013).","journal-title":"J. Chem. Inf. Model."},{"key":"2117_CR20","doi-asserted-by":"publisher","first-page":"4011","DOI":"10.1016\/j.bmc.2013.04.019","volume":"21","author":"D Marcotte","year":"2013","unstructured":"Marcotte, D. et al. Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism. Bioorg. Med. Chem. 21, 4011\u20134019 (2013).","journal-title":"Bioorg. Med. Chem."},{"key":"2117_CR21","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1080\/17460441.2017.1346608","volume":"12","author":"SA Andrei","year":"2017","unstructured":"Andrei, S. A. et al. Stabilization of protein\u2013protein interactions in drug discovery. Expert Opin. Drug Discov. 12, 925\u2013940 (2017).","journal-title":"Expert Opin. Drug Discov."},{"key":"2117_CR22","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1021\/acs.jcim.6b00740","volume":"57","author":"M Ragoza","year":"2017","unstructured":"Ragoza, M., Hochuli, J., Idrobo, E., Sunseri, J. & Koes, D. R. Protein-ligand scoring with convolutional neural networks. J. Chem. Inf. Model. 57, 942\u2013957 (2017).","journal-title":"J. Chem. Inf. Model."},{"key":"2117_CR23","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1021\/ar500432k","volume":"48","author":"JL Reymond","year":"2015","unstructured":"Reymond, J. L. The chemical space project. Acc. Chem. Res. 48, 722\u2013730 (2015).","journal-title":"Acc. Chem. Res."},{"key":"2117_CR24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","volume":"3","author":"NM O\u2019Boyle","year":"2011","unstructured":"O\u2019Boyle, N. M. et al. Open Babel: an open chemical toolbox. J. Cheminform. 3, 33 (2011).","journal-title":"J. Cheminform."},{"key":"2117_CR25","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris, G. M. et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785\u20132791 (2009).","journal-title":"J. Comput. Chem."},{"key":"2117_CR26","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/978-1-60761-670-2_4","volume":"627","author":"SQ Hutsell","year":"2010","unstructured":"Hutsell, S. Q., Kimple, R. J., Siderovski, D. P., Willard, F.S. & Kimple, A. J. High-affinity immobilization of proteins using biotin- and GST-based coupling strategies. Methods Mol. Biol. 627, 75\u201390 (2010).","journal-title":"Methods Mol. Biol."},{"key":"2117_CR27","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1177\/1087057108314651","volume":"13","author":"MD H\u00e4m\u00e4l\u00e4inen","year":"2008","unstructured":"H\u00e4m\u00e4l\u00e4inen, M. D. et al. Label-free primary screening and affinity ranking of fragment libraries using parallel analysis of protein panels. J. Biomol. Screen. 13, 202\u2013209 (2008).","journal-title":"J. Biomol. Screen."},{"key":"2117_CR28","doi-asserted-by":"crossref","unstructured":"Hulme, E. C. (ed.) Receptor\u2013Ligand Interactions: A Practical Approach (Oxford Univ. Press, 1992).","DOI":"10.1093\/oso\/9780199630905.001.0001"},{"key":"2117_CR29","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1002\/anie.200905660","volume":"49","author":"P Gans","year":"2010","unstructured":"Gans, P. et al. Stereospecific isotopic labeling of methyl groups for NMR spectroscopic studies of high-molecular-weight proteins. Angew. Chem. Int. Ed. 49, 1958\u20131962 (2010).","journal-title":"Angew. Chem. Int. Ed."},{"key":"2117_CR30","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.ejmech.2018.01.063","volume":"146","author":"M Lu","year":"2018","unstructured":"Lu, M. et al. Discovery of a Keap1-dependent peptide PROTAC to knockdown Tau by ubiquitination-proteasome degradation pathway. Eur. J. Med. Chem. 146, 251\u2013259 (2018).","journal-title":"Eur. J. Med. Chem."},{"key":"2117_CR31","doi-asserted-by":"publisher","first-page":"7076","DOI":"10.1021\/acs.jmedchem.5b01105","volume":"58","author":"JJ Irwin","year":"2015","unstructured":"Irwin, J. J. et al. An aggregation advisor for ligand discovery. J. Med. Chem. 58, 7076\u20137087 (2015).","journal-title":"J. Med. Chem."},{"key":"2117_CR32","doi-asserted-by":"publisher","first-page":"5142","DOI":"10.1021\/jm400535b","volume":"56","author":"SR LaPlante","year":"2013","unstructured":"LaPlante, S. R. et al. Compound aggregation in drug discovery: implementing a practical NMR assay for medicinal chemists. J. Med. Chem. 56, 5142\u20135150 (2013).","journal-title":"J. Med. Chem."},{"key":"2117_CR33","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1021\/jm901137j","volume":"53","author":"JB Baell","year":"2010","unstructured":"Baell, J. B. & Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem. 53, 2719\u20132740 (2010).","journal-title":"J. Med. Chem."},{"key":"2117_CR34","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1021\/acschembio.7b00903","volume":"13","author":"JB Baell","year":"2018","unstructured":"Baell, J. B. & Nissink, J. W. M. Seven year itch: pan-assay interference compounds (PAINS) in 2017\u2014utility and limitations. ACS Chem. Biol. 13, 36\u201344 (2018).","journal-title":"ACS Chem. Biol."},{"key":"2117_CR35","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1021\/acs.jcim.6b00465","volume":"57","author":"SJ Capuzzi","year":"2017","unstructured":"Capuzzi, S. J., Muratov, E. N. & Tropsha, A. Phantom PAINS: problems with the utility of alerts for pan-assay interference compounds. J. Chem. Inf. Model. 57, 417\u2013427 (2017).","journal-title":"J. Chem. Inf. Model."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-2117-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-2117-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-020-2117-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T17:41:27Z","timestamp":1722534087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-020-2117-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,9]]},"references-count":35,"journal-issue":{"issue":"7805","published-print":{"date-parts":[[2020,4,30]]}},"alternative-id":["2117"],"URL":"https:\/\/doi.org\/10.1038\/s41586-020-2117-z","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737510514.793573161","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,9]]},"assertion":[{"value":"5 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"I.I., D.S.R. and Y. S. Malets work for Enamine, a company that is involved in the synthesis and distribution of drug-like compounds. Y. S. Moroz is a scientific advisor for Enamine.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}