Determinants of protein function revealed by combinatorial entropy optimization

Genome Biol. 2007;8(11):R232. doi: 10.1186/gb-2007-8-11-r232.


We use a new algorithm (combinatorial entropy optimization [CEO]) to identify specificity residues and functional subfamilies in sets of proteins related by evolution. Specificity residues are conserved within a subfamily but differ between subfamilies, and they typically encode functional diversity. We obtain good agreement between predicted specificity residues and experimentally known functional residues in protein interfaces. Such predicted functional determinants are useful for interpreting the functional consequences of mutations in natural evolution and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Combinatorial Chemistry Techniques*
  • Entropy*
  • Evolution, Molecular
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / physiology*
  • Humans
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid


  • Cell Cycle Proteins
  • GTP Phosphohydrolases