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

  • Morcos F
  • Schafer N
  • Cheng R
 et al. 
  • 155


    Mendeley users who have this article in their library.
  • 44


    Citations of this article.


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. We show 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 Tsel are well below the experimental folding temperatures, indicating that the energy landscapes of natural foldable proteins are strongly funneled toward the native state.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • F. Morcos

  • N. P. Schafer

  • R. R. Cheng

  • J. N. Onuchic

  • P. G. Wolynes

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free