Folding the proteome

Trends Biochem Sci. 2013 Jul;38(7):337-44. doi: 10.1016/j.tibs.2013.05.001. Epub 2013 Jun 11.


Protein folding is an essential prerequisite for protein function and hence cell function. Kinetic and thermodynamic studies of small proteins that refold reversibly were essential for developing our current understanding of the fundamentals of protein folding mechanisms. However, we still lack sufficient understanding to accurately predict protein structures from sequences, or the effects of disease-causing mutations. To date, model proteins selected for folding studies represent only a small fraction of the complexity of the proteome and are unlikely to exhibit the breadth of folding mechanisms used in vivo. We are in urgent need of new methods - both theoretical and experimental - that can quantify the folding behavior of a truly broad set of proteins under in vivo conditions. Such a shift in focus will provide a more comprehensive framework from which to understand the connections between protein folding, the molecular basis of disease, and cell function and evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Models, Molecular*
  • Protein Folding*
  • Proteome / chemistry*
  • Proteome / metabolism


  • Escherichia coli Proteins
  • Proteome