{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:48:33Z","timestamp":1775753313627,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP22K21343"],"award-info":[{"award-number":["JP22K21343"]}]},{"name":"JSPS Core-to-Core Program","award":["JPJSCCA20240006"],"award-info":[{"award-number":["JPJSCCA20240006"]}]},{"name":"JST-CREST program","award":["JP MJCR20H8"],"award-info":[{"award-number":["JP MJCR20H8"]}]},{"name":"Japan Agency for Medical Research and Development (AMED","award":["JP223fa727002"],"award-info":[{"award-number":["JP223fa727002"]}]},{"name":"Japan Agency for Medical Research and Development (AMED","award":["JP223fa627001"],"award-info":[{"award-number":["JP223fa627001"]}]},{"name":"Japan Agency for Medical Research and Development (AMED","award":["JP24ama121033"],"award-info":[{"award-number":["JP24ama121033"]}]},{"name":"Japan Agency for Medical Research and Development (AMED","award":["JP223fa627009"],"award-info":[{"award-number":["JP223fa627009"]}]},{"name":"Japan Agency for Medical Research and Development (AMED","award":["JP25jf0126002"],"award-info":[{"award-number":["JP25jf0126002"]}]},{"name":"Japan Agency for Medical Research and Development (AMED","award":["JP25wm0325075"],"award-info":[{"award-number":["JP25wm0325075"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibody engineering is often achieved through laborious mutagenesis and screening. However, the physicochemical basis of cross-reactivity-enhancing mutations remains unclear. We computationally redesigned the severe acute respiratory syndrome coronavirus (SARS-CoV)-1 neutralizing antibody m396 to recognize the SARS-CoV-2 receptor-binding domain (RBD) and characterized its biophysical properties. A first-generation variant carrying three light-chain substitutions (S30LW, S93LI and S94LF) acquired detectable SARS-CoV-2 RBD binding, while strengthening its affinity for the SARS-CoV RBD. A second-generation variant carrying two substitutions (T52HL and L54HW) further improved SARS-CoV-2 binding with a low micromolar affinity, predominantly driven by an approximately 200-fold increase in the association rate. Circular dichroism spectra indicated preserved global folding across the variants, whereas differential scanning calorimetry revealed stepwise decreases in lower-temperature unfolding transitions. Hydrogen\u2013deuterium exchange mass spectrometry showed increased dynamics of CDR-L1 and localized rigidification near CDR-H2 in the second variant. These results suggest a biophysical model in which a small number of mutations reprogram cross-recognition by redistributing the local conformational dynamics.<\/jats:p>","DOI":"10.1093\/jb\/mvag018","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T12:47:09Z","timestamp":1773233229000},"page":"259-267","source":"Crossref","is-referenced-by-count":0,"title":["Observation of redistribution for local conformational dynamics in cross-reactive antibody design"],"prefix":"10.1093","volume":"179","author":[{"given":"Yoshiki","family":"Yasuda","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0794-3963","authenticated-orcid":false,"given":"Satoru","family":"Nagatoishi","sequence":"additional","affiliation":[{"name":"Medical Device Development and Regulation Research Center, Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiei","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University , 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 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Chemistry and Biotechnology, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 ,","place":["Japan"]},{"name":"Medical Device Development and Regulation Research Center, Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 ,","place":["Japan"]},{"name":"Department of Bioengineering, School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 ,","place":["Japan"]},{"name":"Institute of Medical Science, The University of Tokyo , 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"2026040911513701100_ref1","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.cell.2022.05.029","article-title":"Designing antibodies as 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