{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:21:48Z","timestamp":1788398508861,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,7,29]]},"abstract":"<jats:p>Molecular docking is increasingly used to infer aptamer\u2013target interactions, yet most studies rely on computationally predicted aptamer structures rather than experimentally determined ones. Using a benchmark set of aptamers with known high\u2010resolution structures, we show that commonly used modeling approaches, including RNAComposer and AlphaFold3, fail to reliably reproduce aptamer conformations, particularly at the binding sites critical for molecular recognition. Key limitations include the use of A\u2010form RNA models to represent B\u2010form DNA structures, the prediction of ligand\u2010free rather than ligand\u2010bound conformations, and the scarcity of experimentally determined aptamer structures for training machine\u2010learning models. Using the theophylline aptamer, for which high\u2010resolution structures are available in both DNA and RNA forms, we systematically evaluated each step of the standard docking workflow. We found that structure\u2010prediction errors generate incorrect binding pockets, docking scores fail to distinguish theophylline from caffeine despite a 250,000\u2010fold difference in affinity, and molecular dynamics simulations do not overcome these shortcomings. Together, these results reveal fundamental weaknesses in current aptamer docking workflows and caution against using docking\u2010derived models to infer binding mechanisms in the absence of experimental structural data.<\/jats:p>","DOI":"10.1002\/cbic.70481","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:15:53Z","timestamp":1784895353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reconsidering Molecular Docking Practices in Aptamer Research"],"prefix":"10.1002","volume":"27","author":[{"given":"Yachen","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Chemistry Waterloo Institute for Nanotechnology University of Waterloo  Waterloo Ontario 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