Issue 101, 2015

Identification of novel JMJD2A inhibitor scaffold using shape and electrostatic similarity search combined with docking method and MM-GBSA approach

Abstract

We present a hierarchical workflow combining shape- and electrostatic-based virtual screening for the identification of novel Jumonji domain-containing protein 2A (JMJD2A) inhibitors. Our virtual screening protocol initially involved the identification of small molecules, which had similar shape and electrostatic properties to 5-carboxy-8-hydroxyquinoline (5-carboxy-8-HQ, IOX-1). Molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) rescoring were then used to prioritize these small molecules for Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) assay. Compounds contained a catechol scaffold displayed inhibition activity against JMJD2A. They also exhibited competitive inhibition with respect to 2-oxoglutaric acid (2OG). Our study suggested that the novel structure discovered in the present study may serve as a starting point for developing JMJD2A inhibitors.

Graphical abstract: Identification of novel JMJD2A inhibitor scaffold using shape and electrostatic similarity search combined with docking method and MM-GBSA approach

Supplementary files

Article information

Article type
Paper
Submitted
20 Jun 2015
Accepted
23 Sep 2015
First published
23 Sep 2015

RSC Adv., 2015,5, 82936-82946

Identification of novel JMJD2A inhibitor scaffold using shape and electrostatic similarity search combined with docking method and MM-GBSA approach

T. Feng, W. Chen, D. Li, H. Lin, F. Liu, Q. Bao, Y. Lei, X. Zhang, X. Xu, X. Guo, Q. You and H. Sun, RSC Adv., 2015, 5, 82936 DOI: 10.1039/C5RA11896D

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