Ligand-Based Virtual Screening for the Discovery of Inhibitors for Protein Arginine Deiminase Type 4 (PAD4)Chian Ying Teo1, Mohd Basyaruddin Abdul Rahman1, Adam Leow Thean Chor2, Abu Bakar Salleh3, Pedro J Ballester4 and Bimo A Tejo1*
- *Corresponding Author:
- Bimo A Tejo
Department of Chemistry, Faculty of Science
Universiti Putra Malaysia, 43400 UPM Serdang, Malaysia
E-mail: [email protected], [email protected]
Received date: May 02, 2013; Accepted date: June 26, 2013; Published date: July 03, 2013
Citation: Teo CY, Abdul Rahman MB, Thean Chor AL, Salleh AB, Ballester PJ, et al. (2013) Ligand-Based Virtual Screening for the Discovery of Inhibitors for Protein Arginine Deiminase Type 4 (PAD4). Metabolomics 3:118. doi:10.4172/2153-0769.1000118
Copyright: © 2013 Teo CY, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Protein Arginine Deiminase type 4 (PAD4) is a new therapeutic target for the treatment of rheumatoid arthritis. In this study, ligand-based virtual screening with the integration with drug repurposing strategy was applied to the discovery of PAD4 inhibitors. Ultrafast Shape Recognition (USR) was used to search for compounds with similar shape to a previously reported inhibitor with harmful side-effects, i.e., streptonigrin. Thirty five lead-like compounds and two existing drugs were obtained from virtual screening and their inhibitory activity was tested at fixed concentration of 100 μM. Five lead-like compounds showed significant inhibition on the enzymatic activity of PAD4. The potency of the best compound was investigated by carrying out IC50 study. Importantly, the structure of the best of these new active molecules was strikingly different from that of streptonigrin. Furthermore, this new PAD4 inhibitor is the most potent to date found by a computational approach and its structure can be optimized in the future for the design of an even better inhibitor of PAD4.