Acta Pharm. 71 (2021) 33-56

 

full paper

Original research paper

 

In silico data mining of large-scale databases for the virtual screening of human interleukin-2 inhibitors

SOBIA AHSAN HALIM, ZAHEER-UL-HAQ, AJMAL KHAN, AHMED AL-RAWAHI and AHMED AL-HARRASI

sobia_halim@unizwa.edu.om; aharrasi@unizwa.edu.om

1 Natural and Medical Science Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman

2 Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, 75270 Karachi, Pakistan

Accepted March 8, 2020

Published online April 21, 2020

 

Interleukin-2 (IL-2) is involved in the activation and differentiation of T-helper cells. Uncontrolled activated T cells play a key role in the pathophysiology by stimulating inflammation and autoimmune diseases like arthritis, psoriasis and Crohn’s disease. T cells activation can be suppressed either by preventing IL-2 production or blocking the IL-2 interaction with its receptor. Hence, IL-2 is now emerging as a target for novel therapeutic approaches in several autoimmune disorders. This study was carried out to set up an effective virtual screening (VS) pipeline for IL-2. Four docking/scoring approaches (FRED, MOE, GOLD and Surflex-Dock) were compared in the re-docking process to test their performance in producing correct binding modes of IL-2 inhibitors. Surflex-Dock and FRED were the best in predicting the native pose in its top-ranking position. Shapegauss and CGO scoring functions identified the known inhibitors of IL-2 in top 1, 5 and 10 % of library and differentiated binders from non-binders efficiently with average AUC of > 0.9 and > 0.7, resp. The applied docking protocol served as a basis for the VS of a large database that will lead to the identification of more active compounds against IL-2.

 

Keywords: IL-2, virtual screening, Fred, Moe, Gold, Surflex-Dock, ROC-curves