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Updated: Jul 16, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Sequence-specific dynamics modulate recognition specificity in WW domains
Tao Peng1, John S Zintsmaster, Andrew T Namanja
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 USA.
Abstract:
The current canon attributes the binding specificity of protein-recognition motifs to distinctive chemical moieties in their constituent amino acid sequences. However, we show for a WW domain that the sequence crucial for specificity is an intrinsically flexible loop that partially rigidifies upon ligand docking. A single-residue deletion in this loop simultaneously reduces loop flexibility and ligand binding affinity. These results suggest that sequences of recognition motifs may reflect natural selection of not only chemical properties but also dynamic modes that augment specificity.
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