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This article is part of the supplement: Eleventh International Conference on Bioinformatics (InCoB2012): Bioinformatics

Open Access Proceedings

Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure-based virtual screening

Chian Ying Teo1, Steven Shave2, Adam Leow Thean Chor3, Abu Bakar Salleh4, Mohd Basyaruddin Bin Abdul Rahman1, Malcolm D Walkinshaw2 and Bimo A Tejo1*

Author Affiliations

1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Malaysia

2 Structural Biochemistry Group, The University of Edinburgh, Michael Swann Building, King's Buildings, Edinburgh, EH9 3JR, UK

3 Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Malaysia

4 Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Malaysia

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BMC Bioinformatics 2012, 13(Suppl 17):S4  doi:10.1186/1471-2105-13-S17-S4

Published: 13 December 2012



Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Anticitrullinated protein autoantibody has been documented as a highly specific autoantibody associated with RA. Protein arginine deiminase type 4 (PAD4) is the enzyme responsible for catalyzing the conversion of peptidylarginine into peptidylcitrulline. PAD4 is a new therapeutic target for RA treatment. In order to search for inhibitors of PAD4, structure-based virtual screening was performed using LIDAEUS (Ligand discovery at Edinburgh university). Potential inhibitors were screened experimentally by inhibition assays.


Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC50 values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.


Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.