Kinetics are probe-dependent during downhill folding of an engineered λ6-85 protein

Hairong Ma, Martin Gruebele

Research output: Contribution to journalArticlepeer-review


The Y22W/Q33Y/G46,48A mutant of the protein λ6-85 folds in a few microseconds at room temperature. We find that its folding kinetics are probe-dependent under a strong bias toward the native state, a new signature for downhill folding. The IR- and fluorescence-detected relaxation time scales converge when the native bias is removed by raising the temperature, recovering activated two-state folding. Langevin dynamics simulations on one- and 2D free energy surfaces tunable from two-state to downhill folding reproduce the difference between the IR and fluorescence experiments, as well as the temperature and viscosity trends. In addition, the 2D surface reproduces the stretched exponential dynamics that we fit to the glucose solution experimental data at short times. Nonexponential dynamics at < 10 μs is a signature either for local free energy minima along the reaction coordinate ("longitudinal roughness"), or for folding on a higher-dimensional free energy surface ("transverse roughness").

Original languageEnglish (US)
Pages (from-to)2283-2287
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
StatePublished - Feb 15 2005


  • Amide band
  • Fluorescence
  • Helix bundle
  • Infrared
  • Landscape roughness

ASJC Scopus subject areas

  • General


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