%0 Journal Article
%T Accidental Interaction between PDZ Domains and Diclofenac Revealed by NMR-Assisted Virtual Screening
%A Takeshi Tenno
%A Natsuko Goda
%A Yoshitaka Umetsu
%A Motonori Ota
%A Kengo Kinoshita
%A Hidekazu Hiroaki
%J Molecules
%D 2013
%I MDPI AG
%R 10.3390/molecules18089567
%X 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¨Cligand 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¨Cdiclofenac interaction were also determined. Pharmacological implications of the accidental PDZ¨Cdiclofenac interaction are further discussed.
%K PDZ domains
%K protein¨Cprotein interaction inhibitor
%K non-steroidal anti-inflammatory drug
%K drug repositioning
%U http://www.mdpi.com/1420-3049/18/8/9567