Identification of novel JMJD2A inhibitor scaffold using shape and electrostatic similarity search combined with docking method and MM-GBSA approach. Issue 101 (30th September 2015)

• Record Type: Journal Article
• Authors: Feng, Taotao; Chen, Weilin; Li, Dongdong; Lin, Hongzhi; Liu, Fang; Bao, Qichao; Lei, Yonghua; Zhang, Xiaojin; Xu, Xiaoli; Guo, Xiaoke; You, Qidong; Sun, Haopeng
• Is Part Of: RSC advances. Volume 5:Issue 101(2015)
• Page Start: 82936
• Page End: 82946
• Publication Date: 2015-09-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c5ra11896d
• Languages: English
• ISSNs: 2046-2069

Abstract

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. 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.