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Diverse screening methodologies are employed, including DNA\u2010encoded library technology, high\u2010throughput screening, and fragment\u2010based drug discovery (FBDD). Among these, FBDD is particularly powerful when integrated with structure\u2010guided drug design and biophysical affinity measurements. However, accurately quantifying the weak binding affinities of fragments remains a significant challenge. To address this, we introduce chemical shift anisotropy  (CSAKD), a novel method for determining absolute fragment affinities using  NMR relaxation. The CSAKD approach eliminates the need for titration experiments and isotopic labeling. Furthermore, we complement this method with a machine learning model for the rapid and accurate prediction of  chemical shielding tensors. In summary, CSAKD allows fast and efficient affinity determination which seamlessly integrates into FBDD by \u00a0NMR.<\/jats:p>","DOI":"10.1002\/anie.6036832","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:28:21Z","timestamp":1781263701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CSAKD: Determining Absolute Ligand Affinities From\n                    <sup>19<\/sup>\n                    F NMR Chemical Shift Anisotropy"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1107-6196","authenticated-orcid":false,"given":"Simon H.","family":"R\u00fcdisser","sequence":"first","affiliation":[{"name":"Department of Biology ETH Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-6427","authenticated-orcid":false,"given":"Gabriela","family":"Stadler","sequence":"additional","affiliation":[{"name":"Department of Biology ETH Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-495X","authenticated-orcid":false,"given":"Alvar D.","family":"Gossert","sequence":"additional","affiliation":[{"name":"Department of Biology ETH Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.armc.2017.08.004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2220"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2008.11.007"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2010.04.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.07.013"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml900002k"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2014.09.007"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2606"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01210"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja905207t"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja034646d"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm011122k"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200903528"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026033392705"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10858-020-00325-x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1304045110"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110380455"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20020802)41:15<2644::AID-ANIE2644>3.0.CO;2-O"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmre.2000.2170"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00381a010"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00381a009"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","unstructured":"T. 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