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- Title
Accidental Interaction between PDZ Domains and Diclofenac Revealed by NMR-Assisted Virtual Screening.
- Authors
Takeshi Tenno; Natsuko Goda; Yoshitaka Umetsu; Motonori Ota; Kengo Kinoshita; Hidekazu Hiroaki
- Abstract
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.
- Subjects
PROTEIN-ligand interactions; ANTI-inflammatory agents; CHEMICAL synthesis; PDZ proteins; DICLOFENAC; SEARCH algorithms; PHARMACOLOGY
- Publication
Molecules, 2013, Vol 18, Issue 8, p9567
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules18089567