Evolutionarily conserved pathways of energetic connectivity in protein families.
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.
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Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
Ranganathan
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D008958:Models, Molecular; D009154:Mutation; D011336:Probability; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D013223:Statistics as Topic; D013816:Thermodynamics
D000596:Amino Acids; D011506:Proteins; D011993:Recombinant Fusion Proteins