title: Phage display can select over-hydrophobic sequences that may impair prediction of natural domain-peptide interactions.
abstract: BACKGROUND
  The phage display peptide selection approach is widely used for defining binding specificities of globular domains. PDZ domains recognize partner proteins via C-terminal motifs and are often used as a model for interaction predictions. Here, we investigated to which extent phage display data that were recently published for 54 human PDZ domains can be applied to the prediction of human PDZ-peptide interactions.
  
  
  RESULTS
  Promising predictions were obtained for one-third of the 54 PDZ domains. For the other two-thirds, we detected in the phage display peptides an important bias for hydrophobic amino acids that seemed to impair correct predictions. Therefore, phage display-selected peptides may be over-hydrophobic and of high affinity, while natural interaction motifs are rather hydrophilic and mostly combine low affinity with high specificity. We suggest that potential amino acid composition bias should systematically be investigated when applying phage display data to the prediction of specific natural domain-linear motif interactions.
authors.affiliation: Oncoproteins, Unité CNRS-UDS UMR 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France. katja.luck@unistra.fr
authors.forename: Katja
authors.initials: K
authors.lastname: Luck
authors.forename: Gilles
authors.initials: G
authors.lastname: Travé
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D054731:PDZ Domains; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs
chemical_list: D000596:Amino Acids; D019151:Peptide Library; D010455:Peptides