Dynamic-Structure Redesign of Calmodulin Reveals Mechanistic Constraints on Ryr2 Regulation
leak in a disease-relevant model. These findings show that improved binding affinity alone is insufficient to enhance physiological regulation and that successful CaM redesign requires preservation of conformational dynamics. More broadly, they demonstrate that integrating conformational dynamics into protein redesign can enable functionally predictive engineering of flexible regulatory protein-protein interactions.
Authors
- Sándor Györke (ORCID: https://orcid.org/0000-0002-0821-1983)
- Rǎzvan L. Cornea (ORCID: https://orcid.org/0000-0001-5739-0992)
- Daniel J. Blackwell (ORCID: https://orcid.org/0000-0001-6619-1792)
- Melanie L. Aprahamian
- Peter M. Kekenes–Huskey (ORCID: https://orcid.org/0000-0001-7286-3022)
- Md Nure Alam Afsar (ORCID: https://orcid.org/0000-0002-7251-7661)
- Robyn T. Rebbeck (ORCID: https://orcid.org/0000-0003-3840-2286)
- Vladimir Bogdanov (ORCID: https://orcid.org/0000-0001-9287-5303)
- Jonathan P. Davis (ORCID: https://orcid.org/0000-0002-5627-1550)
- B Knollmann
- Steffen Lindert
- Christopher N. Johnson
- Aleksei Chekodanov
- Svetlana Tikunova
- Nicolas Fadell
Institutions
- University of Minnesota (US)
- University of California, Los Angeles (US)
- Loyola University Chicago (US)
- The Ohio State University Wexner Medical Center (US)
- The Ohio State University (US)
- Independent University of Moscow (RU)
- Vanderbilt University Medical Center (US)
- Mississippi State University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-17
- DOI
- https://doi.org/10.64898/2026.04.14.717973
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 0.00