Coevolutionary information, protein folding landscapes, and the thermodynamics of natural selection

Faruck Morcos, Nicholas P. Schafer, Ryan R. Cheng, José N. Onuchic, Peter G. Wolynes

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


The energy landscape used by nature over evolutionary timescales to select protein sequences is essentially the same as the one that folds these sequences into functioning proteins, sometimes in microseconds. Weshow that genomic data, physical coarse-grained free energy functions, and family-specific information theoretic models can be combined to give consistent estimates of energy landscape characteristics of natural proteins. One such characteristic is the effective temperature Tsel at which these foldable sequences have been selected in sequence space by evolution. Tsel quantifies the importance of folded-state energetics and structural specificity for molecular evolution. Across all protein families studied, our estimates for T sel are well below the experimental folding temperatures, indicating that the energy landscapes of natural foldable proteins are strongly funneled toward the native state.

Original languageEnglish
Pages (from-to)12408-12413
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
StatePublished - Aug 26 2014


  • Elastic effects
  • Energy landscape theory
  • Funneled landscapes
  • Information theory
  • Selection temperature

ASJC Scopus subject areas

  • General


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