Virtual screening of B-Raf kinase inhibitors: A combination of pharmacophore modelling,molecular docking, 3D-QSAR model and binding free energy calculation studies |
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Affiliation: | 1. Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Taiyuan 030006, China;2. Department of Pharmacy, Shanxi Medical University, Taiyuan 030006, China |
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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 (ΔGbind) 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. |
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Keywords: | B-Raf kinase inhibitors Virtual screening Pharmacophore Molecular docking 3D QSAR Binding free energy calculation |
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