Quantifying protein folding transition states with ΦT

J. Ervin, M. Gruebele

Research output: Contribution to journalArticlepeer-review


A number of reaction coordinates have been proposed for reduced-dimensionality representations of a protein's folding free energy surface. We discuss in detail the entropic reaction coordinate ΦT = Δ S/ΔS, recently introduced to quantify the conservation of mutations and the location of the folding transition state based on experimental temperature-tuning data. Numerical simulations illustrate the advantages as well as the limitations of ΦT · ΦT can be determined from experiment, computation, and analytical theory; ΦT can also be used to investigate structurally localized perturbations of the free energy surface. However, ΦT is only a relative reaction cordinate; furthermore, proteins undergo cold denaturation at sufficiently low temperatures, and care must be taken in interpreting ΦT near the region where ∂ ΔG/∂T = 0, particularly if the heat capacity change upon folding is small.

Original languageEnglish (US)
Pages (from-to)115-128
Number of pages14
JournalJournal of Biological Physics
Issue number2
StatePublished - 2002


  • Free energy
  • Kramers model
  • Phi-value analysis
  • Reaction coordinate
  • Ubiquitin

ASJC Scopus subject areas

  • Biophysics
  • Atomic and Molecular Physics, and Optics
  • Molecular Biology
  • Cell Biology


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