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March 26, 20260 citationsOpen Access

Dielectric confinement contribution to the folding free energy of transmembrane proteins

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EPE. F. Perez-Eugenio

Key Points

  • The study aims to explore how electromagnetic self-energy and dielectric confinement contribute to the folding free energy of transmembrane proteins.
  • Predicted folding free energy based on dielectric confinement.
  • Evaluated the effect of membrane thickness on electromagnetic fluctuations.
  • Used differential scanning calorimetry for detection.
  • Applied a systematic experimental protocol with rhomboid protease GlpG in various membranes.
  • Identified a thickness-dependent component of folding free energy scaling as 1/d³.
  • Demonstrated the impact of membrane thickness on protein folding behavior.
  • Provided a methodological framework for future experimental investigations.

Abstract

We predict that the folding free energy of a transmembrane protein contains a contribution from electromagnetic self-energy that depends on the thickness of the host membrane. The mechanism is dielectric confinement: a lipid bilayer surrounded by water modifies the electromagnetic fluctuation spectrum accessible to a polarizable protein embedded within it. The thickness-dependent component scales as 1/d³, detectable by differential scanning calorimetry. We propose an experimental protocol using the rhomboid protease GlpG reconstituted in five membranes of systematically varying thickness (DLPC to DAPC). Repository includes LaTeX source, compiled PDFs, calculation script, and figures.

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Cite This Study

E. F. Perez-Eugenio (2026) studied this question.

synapsesocial.com/papers/69c4cd25fdc3bde448919078https://doi.org/10.5281/zenodo.19202897
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