Evolutionarily conserved pathways of energetic connectivity in protein families

Science. 1999 Oct 8;286(5438):295-9. doi: 10.1126/science.286.5438.295.


For mapping energetic interactions in proteins, a technique was developed that uses evolutionary data for a protein family to measure statistical interactions between amino acid positions. For the PDZ domain family, this analysis predicted a set of energetically coupled positions for a binding site residue that includes unexpected long-range interactions. Mutational studies confirm these predictions, demonstrating that the statistical energy function is a good indicator of thermodynamic coupling in proteins. Sets of interacting residues form connected pathways through the protein fold that may be the basis for efficient energy conduction within proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Binding Sites
  • Conserved Sequence
  • Evolution, Molecular*
  • Models, Molecular
  • Mutation
  • Probability
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Statistics as Topic
  • Thermodynamics


  • Amino Acids
  • Proteins
  • Recombinant Fusion Proteins