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Annual Review of Biophysics

Volume 54, 2025

Protein Modeling with DEER Spectroscopy

  • Maxx H. Tessmer1 and Stefan Stoll1
  • Department of Chemistry, University of Washington, Seattle, Washington, USA; email: [email protected]
  • Vol. 54:35-57 (Volume publication date May 2025)
  • First published as a Review in Advance on December 17, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

Double electron–electron resonance (DEER) combined with site-directed spin labeling can provide distance distributions between selected protein residues to investigate protein structure and conformational heterogeneity. The utilization of the full quantitative information contained in DEER data requires effective protein and spin label modeling methods. Here, we review the application of DEER data to protein modeling. First, we discuss the significance of spin label modeling for accurate extraction of protein structural information and review the most popular label modeling methods. Next, we review several important aspects of protein modeling with DEER, including site selection, how DEER restraints are applied, common artifacts, and the unique potential of DEER data for modeling structural ensembles and conformational landscapes. Finally, we discuss common applications of protein modeling with DEER data and provide an outlook.

Keyword(s): DEER, EPR spectroscopy, integrative modeling, spin labeling
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2025-05-06
2025-06-18
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Protein Modeling with DEER Spectroscopy
Annual Review of Biophysics 54, 35 (2025); https://doi.org/10.1146/annurev-biophys-030524-013431
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