Encyclopedia of Biophysics

Living Edition
| Editors: Gordon Roberts, Anthony Watts, European Biophysical Societies

Protein Folding, Energy Landscapes and Downhill Protein Folding Scenarios

  • Christopher M. JohnsonEmail author
  • Timothy D. Sharpe
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-35943-9_10068-1



In 1968 Levinthal identified the disparity between the experimentally observed timescale of protein folding reactions and the astronomical complexity of an unguided conformational search for the native state. It was once thought that rapid folding required a unique pathway to the native conformation. However, in recent years, the discussion has seemingly shifted from “how do proteins fold so quickly?” to “why do many proteins fold so slowly?”. New perspectives on the folding process have led to an understanding that finding the native conformation is to some extent energetically downhill and, in the absence of complicating factors, can proceed rapidly by a multiplicity of parallel routes.

Also in the 1960s, it was established that protein folding was apparently a cooperative “all or none” process. This interpretation has also been challenged in recent years, and there is now considerable discussion (Muñoz et...


Downhill Folding Peripheral Subunit-binding Domain (PSBDs) Time Constant Limits Energy Landscape Theory smFRET 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Crown 2018

Authors and Affiliations

  1. 1.MRC Laboratory of Molecular BiologyCambridgeUK
  2. 2.Biophysics Facility, BiozentrumUniversity of BaselBaselSwitzerland

Section editors and affiliations

  • Alan Cooper
    • 1
  1. 1.School of Chemistry, University of GlasgowGlasgowUK