Entropy capacity determines protein folding

Proteins. 2006 Apr 1;63(1):144-54. doi: 10.1002/prot.20851.


Search and study of the general principles that govern kinetics and thermodynamics of protein folding generate a new insight into the factors controlling this process. Here, based on the known experimental data and using theoretical modeling of protein folding, we demonstrate that there exists an optimal relationship between the average conformational entropy and the average energy of contacts per residue-that is, an entropy capacity-for fast protein folding. Statistical analysis of conformational entropy and number of contacts per residue for 5829 protein structures from four general structural classes (all-alpha, all-beta, alpha/beta, alpha+beta) demonstrates that each class of proteins has its own class-specific average number of contacts (class alpha/beta has the largest number of contacts) and average conformational entropy per residue (class all-alpha has the largest number of rotatable angles phi, psi, and chi per residue). These class-specific features determine the folding rates: alpha proteins are the fastest folding proteins, then follow beta and alpha+beta proteins, and finally alpha/beta proteins are the slowest ones. Our result is in agreement with the experimental folding rates for 60 proteins. This suggests that structural and sequence properties are important determinants of protein folding rates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Computational Biology / methods*
  • Databases, Protein
  • Entropy
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Models, Statistical
  • Models, Theoretical
  • Molecular Conformation
  • Protein Conformation
  • Protein Denaturation
  • Protein Folding*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteomics / methods*
  • Reproducibility of Results
  • Thermodynamics


  • Amino Acids
  • Proteins