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Cited by 1Advanced Fluorescence Microscopy TechniquesProtein Structure and DynamicsPhotochemistry and Electron Transfer Studies

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Barrel Shape and Chromophore Rigidity Predict Fluorescent-Protein Photophysics

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Begg, Luke P., Mason, Madeline L., Zimmer, Marc·2026·Journal of Chemical Information and Modeling
DOI 10.1021/acs.jcim.6c01606PMC PMC13508766

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Abstract

The 11-stranded β-barrel of fluorescent proteins (FPs) is universally conserved, yet its quantitative geometry has not been systematically characterized. We analyzed cross-sectional barrel geometry across 908 FP crystal structures in the RCSB PDB by principal component analysis (PCA)-based axis determination and convex hull analysis of protein-atom slices at the chromophore plane; 780 structures (210–245 residues, with the chromophore-containing chain selected in FP-complex cocrystals) form the canonical analysis cohort. Barrel shape, but not size, correlates with emission wavelength: red-shifted proteins have narrower, more elliptical barrels (ρ = −0.328 for minor axis, p = 2.2 × 10–17). Fluorescence quantum yield, by contrast, is not governed by barrel size: it tracks how rigidly the barrel holds the chromophore (chromophore-to-barrel B-factor ratio, ρ = −0.49 per unique FP), together with the chromophore’s ground-state planarity (ρ = −0.42) as an independent signal of comparable strength. The planarity term is most pronounced among red fluorescent proteins, which span the widest range of ground-state twist. Principal correlations survive Benjamini–Hochberg correction and partial correlation controlling for resolution. The barrel is not a passive scaffold: it constrains chromophore rigidity and thereby shapes photophysical output. The pipeline was developed with Claude (Anthropic) via Claude Code.

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Metadata

Authors
Begg, L. P., Mason, M. L., & Zimmer, M.
Affiliations
Connecticut College (US)
Corresponding author
Zimmer, Marc
ORCID
Zimmer, Marc
Venue
Journal of Chemical Information and Modeling
Publisher
American Chemical Society (ACS)
Published
2026-08-06
Volume
66
Issue
16
Pages
10266-10276
ISSN
  • 1549-9596 (ISSN-L)
  • 1549-960X
DOI
10.1021/acs.jcim.6c01606
PMC
PMC13508766
OpenAlex
W7196943310
Cited by
1
References
44
Citations by year
2026: 1
FWCI
2.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Chemical Information and Modeling (publishedVersion, cc-by)
  • ChemRxiv (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Digital Commons @ Connecticut College (Connecticut College) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Photochemistry and Electron Transfer Studies
Keywords
fluorescent proteins, fluorescence quantum yield, emission wavelength, protein crystal structure
MeSH terms
Luminescent Proteins, Models, Molecular, Principal Component Analysis

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CoChat. (2026). Citation check: Barrel Shape and Chromophore Rigidity Predict Fluorescent-Protein Photophysics. https://app.cochat.ai/papers/10.1021/acs.jcim.6c01606
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Begg, L. P., Mason, M. L., & Zimmer, M. (2026). Barrel Shape and Chromophore Rigidity Predict Fluorescent-Protein Photophysics. Journal of Chemical Information and Modeling. https://doi.org/10.1021/acs.jcim.6c01606