Golden triangle for folding rates of globular proteins

Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):147-50. doi: 10.1073/pnas.1210180110. Epub 2012 Dec 18.

Abstract

The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured rates of spontaneous folding of single-domain globular proteins range from microseconds to hours: the difference (11 orders of magnitude) is akin to the difference between the life span of a mosquito and the age of the universe. Here, we show that physical theory with biological constraints outlines a "golden triangle" limiting the possible range of folding rates for single-domain globular proteins of various size and stability, and that the experimentally measured folding rates fall within this narrow triangle built without any adjustable parameters, filling it almost completely. In addition, the golden triangle predicts the maximal size of protein domains that fold under solely thermodynamic (rather than kinetic) control. It also predicts the maximal allowed size of the "foldable" protein domains, and the size of domains found in known protein structures is in a good agreement with this limit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysics
  • Models, Biological*
  • Models, Molecular*
  • Protein Folding*
  • Protein Structure, Tertiary / physiology*
  • Proteins / metabolism*
  • Thermodynamics

Substances

  • Proteins