{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T20:12:00Z","timestamp":1784923920842,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This paper presents the experimental protein\u2013ligand datasets used as benchmarks in the CASP 16 blind prediction experiment\u2014the first CASP round to incorporate targets from pharmaceutical discovery projects. We have assembled and characterized protein\u2010ligand complexes for four proteins that are known or candidate drug targets: human chymase, human cathepsin G, human autotaxin, and the SARS\u2010CoV\u20102 main protease. The collection encompasses over 200 co\u2010crystal structures at resolutions better than 2.7\u2009\u00c5, paired with binding affinity measurements for approximately 160 compounds covering a broad affinity range (nanomolar to high micromolar). These data enabled the CASP16 pose\u2010prediction and affinity\u2010prediction challenges. Many systems feature potentially challenging characteristics, including chymase's electropositive surface and acidic ligands, which require proper handling of titratable ligand groups; autotaxin complexes with and without zinc coordination; and a SARS\u2010CoV\u20102 protease crystal form exhibiting an unusually open active site conformation. We describe the experimental approaches\u2014from protein production and crystallization to binding assay development\u2014that yielded these reference data. Contributed by scientists at F. Hoffmann\u2010La Roche and Idorsia Pharmaceuticals, these datasets represent actual drug discovery projects and therefore provide a realistic testbed for assessing how computational methods perform on pharmaceutically relevant targets. An accompanying paper in the present special journal issue provides a comprehensive assessment of the pose and affinity predictions for these pharmaceutical protein\u2010ligand systems.<\/jats:p>","DOI":"10.1002\/prot.70053","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T08:58:46Z","timestamp":1759481926000},"page":"79-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The\n                    <scp>CASP<\/scp>\n                    16 Experimental Protein\u2013Ligand Datasets"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-3667","authenticated-orcid":false,"given":"Andreas","family":"Tosstorff","sequence":"first","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0447-1101","authenticated-orcid":false,"given":"Markus G.","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4189-6873","authenticated-orcid":false,"given":"J\u00f6rg","family":"Benz","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-562X","authenticated-orcid":false,"given":"Bernd","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8663-5266","authenticated-orcid":false,"given":"Christian","family":"Kramer","sequence":"additional","affiliation":[{"name":"Roche Pharmaceutical Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3880-7438","authenticated-orcid":false,"given":"May","family":"Sharpe","sequence":"additional","affiliation":[{"name":"Swiss Light Source Paul Scherrer Institute  Villigen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7676-0239","authenticated-orcid":false,"given":"Chia\u2010Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Swiss Light Source Paul Scherrer Institute  Villigen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9634-9033","authenticated-orcid":false,"given":"Alexander","family":"Metz","sequence":"additional","affiliation":[{"name":"Idorsia Pharmaceuticals Ltd. Translational Sciences  Allschwil Switzerland"},{"name":"UCB Biopharma SRL  Braine\u2010l'Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8946-2514","authenticated-orcid":false,"given":"Julien","family":"Hazemann","sequence":"additional","affiliation":[{"name":"Idorsia Pharmaceuticals Ltd. Translational Sciences  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6177-5457","authenticated-orcid":false,"given":"Daniel","family":"Ritz","sequence":"additional","affiliation":[{"name":"Idorsia Pharmaceuticals Ltd. Translational Sciences  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7250-9541","authenticated-orcid":false,"given":"Aengus Mac","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Idorsia Pharmaceuticals Ltd. Translational Sciences  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3375-1738","authenticated-orcid":false,"given":"Michael K.","family":"Gilson","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences University of California san Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","unstructured":"X.Wang J.Sun S.Ahmad et\u00a0al. \u201cEnantioselective Protein Affinity Selection Mass Spectrometry (EAS\u2010MS) \u201dpreprint bioRxiv 2025 https:\/\/doi.org\/10.1101\/2025.01.17.633682.","DOI":"10.1101\/2025.01.17.633682"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.70061"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304087200"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0700619"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01819"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.699535"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21551"},{"key":"e_1_2_10_9_1","unstructured":"D.Banner H.Hilpert B.Kuhn andH.Mauser \u201cVinylogous Acids Derivatives as Chymase Inhibitors (WO2008043698A1) \u201d2008."},{"key":"e_1_2_10_10_1","unstructured":"D.Banner H.Hilpert B.Kuhn andH.Mauser \u201cNovel Fused Pyrrole Derivatives (WO2007068621A1) \u201d2007."},{"key":"e_1_2_10_11_1","unstructured":"D.Banner H.Hilpert B.Kuhn andH.Mauser \u201cNovel Vinylogous Acids Derivatives (WO2007063010A1) \u201d2007."},{"key":"e_1_2_10_12_1","unstructured":"D.Banner H.Mauser R. E.Minder andH. P.Wessel \u201cSulfonamide Derivatives as Chymase Inhibitors (WO2008084004A1) \u201d2008."},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2003.08.040"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057109332595"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444911001314"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444994003112"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904016427"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798319011471"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.141911"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708705200"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/BA20040074"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798324000329"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102223\u2010y"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444911007773"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767313097419"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15123"},{"key":"e_1_2_10_30_1","volume-title":"STARANISO","author":"Tickle I. J.","year":"2018"},{"key":"e_1_2_10_31_1","volume-title":"Grade2, v 1.7.0","author":"Smart O. S.","year":"2021"}],"container-title":["Proteins: Structure, Function, and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prot.70053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T07:42:54Z","timestamp":1767080574000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.70053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/prot.70053"],"URL":"https:\/\/doi.org\/10.1002\/prot.70053","archive":["Portico"],"relation":{},"ISSN":["0887-3585","1097-0134"],"issn-type":[{"value":"0887-3585","type":"print"},{"value":"1097-0134","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]},"assertion":[{"value":"2025-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}