Virtual screening of B-Raf kinase inhibitors: A combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy calculation studies. (October 2017)

• Record Type: Journal Article
• Authors: Zhang, Wen; Qiu, Kai-Xiong; Yu, Fang; Xie, Xiao-Guang; Zhang, Shu-Qun; Chen, Ya-Juan; Xie, Hui-Ding
• Is Part Of: Computational biology and chemistry. Volume 70(2017)
• Page Start: 186
• Page End: 190
• Publication Date: 2017-10
• Subjects: B-Raf kinase inhibitors -- Virtual screening -- Pharmacophore -- Molecular docking -- 3D QSAR -- Binding free energy calculation; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2017.08.017
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: A combined virtual screening of B-Raf inhibitors was performed. Five of six hit compounds show good biological activities (IC50 < 50 μM). Five structurally diverse compounds are expected to develop novel B-Raf inhibitors. Abstract: B-Raf kinase has been identified as an important target in recent cancer treatment. In order to discover structurally diverse and novel B-Raf inhibitors (BRIs), a virtual screening of BRIs against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy (Δ G bind ) calculation studies in this work. After the virtual screening, six promising hit compounds were obtained, which were then tested for inhibitory activities of A375 cell lines. In the result, five hit compounds show good biological activities (IC50 < 50 μM). The present method of virtual screening can be applied to find structurally diverse inhibitors, and the obtained five structurally diverse compounds are expected to develop novel BRIs.