Accidental interaction between PDZ domains and diclofenac revealed by NMR-assisted virtual screening

Takeshi Tenno, Natsuko Goda, Yoshitaka Umetsu, Motonori Ota, Kengo Kinoshita, Hidekazu Hiroaki

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


In silico approaches have become indispensable for drug discovery as well as drug repositioning and adverse effect prediction. We have developed the eF-seek program to predict protein-ligand interactions based on the surface structure of proteins using a clique search algorithm. We have also developed a special protein structure prediction pipeline and accumulated predicted 3D models in the Structural Atlas of the Human Genome (SAHG) database. Using this database, genome-wide prediction of non-peptide ligands for proteins in the human genome was performed, and a subset of predicted interactions including 14 PDZ domains was then confirmed by NMR titration. Surprisingly, diclofenac, a non-steroidal anti-inflammatory drug, was found to be a non-peptide PDZ domain ligand, which bound to 5 of 15 tested PDZ domains. The critical residues for the PDZ-diclofenac interaction were also determined. Pharmacological implications of the accidental PDZ-diclofenac interaction are further discussed.

Original languageEnglish
Pages (from-to)9567-9581
Number of pages15
Issue number8
Publication statusPublished - 2013 Aug


  • Drug repositioning
  • Non-steroidal anti-inflammatory drug
  • PDZ domains
  • Protein-protein interaction inhibitor


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