title: Evolutionarily conserved pathways of energetic connectivity in protein families.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Lockless
authors.forename: R
authors.initials: R
authors.lastname: Ranganathan
mesh_terms: 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
chemical_list: D000596:Amino Acids; D011506:Proteins; D011993:Recombinant Fusion Proteins