Reversible two-state folding of the ultrafast protein gpW under mechanical force

Jörg Schönfelder, David De Sancho, Ronen Berkovich, Robert B. Best, Victor Muñoz, Raul Perez-Jimenez

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Ultrafast folding proteins have limited cooperativity and thus are excellent models to resolve, via single-molecule experiments, the fleeting molecular events that proteins undergo during folding. Here we report single-molecule atomic force microscopy experiments on gpW, a protein that, in bulk, folds in a few microseconds over a marginal folding barrier (∼1 kBT). Applying pulling forces of only 5 pN, we maintain gpW in quasi-equilibrium near its mechanical unfolding midpoint and detect how it interconverts stochastically between the folded and an extended state. The interconversion pattern is distinctly binary, indicating that, under an external force, gpW (un)folds over a significant free-energy barrier. Using molecular simulations and a theoretical model we rationalize how force induces such barrier in an otherwise downhill free-energy surface. Force-induced folding barriers are likely a general occurrence for ultrafast folding biomolecules studied with single-molecule force spectroscopy.

Original languageEnglish
Article number59
JournalCommunications Chemistry
Issue number1
StatePublished - 1 Dec 2018

ASJC Scopus subject areas

  • Materials Chemistry
  • General Chemistry
  • Biochemistry
  • Environmental Chemistry


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