The favourable transfer free energy for a transmembrane (TM) α-helix between the aqueous phase and lipid bilayer underlies the stability of membrane proteins. However, the connection between the energetics and process of membrane protein assembly by the Sec61/SecY translocon complex in vivo is not clear. Here, we directly determine the partitioning free energies of a family of designed peptides using three independent approaches: an experimental microsomal Sec61 translocon assay, a biophysical (spectroscopic) characterization of peptide insertion into hydrated planar lipid bilayer arrays, and an unbiased atomic-detail equilibrium folding-partitioning molecular dynamics simulation. Remarkably, the measured free energies of insertion are quantitatively similar for all three approaches. The molecular dynamics simulations show that TM helix insertion involves equilibrium with the membrane interface, suggesting that the interface may play a role in translocon-guided insertion.

Original languageEnglish
Article number4863
JournalNature Communications
Early online date10 Sept 2014
Publication statusPublished - 10 Sept 2014


  • Amino Acid Motifs
  • Cell Membrane/metabolism
  • Escherichia coli Proteins/metabolism
  • Membrane Proteins/metabolism
  • Molecular Dynamics Simulation
  • Protein Structure, Secondary
  • SEC Translocation Channels
  • Serine Endopeptidases/metabolism
  • Spectrum Analysis
  • Thermodynamics


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