Drug discovery for DNA break repair system by screening from TCM database and molecular dynamics approach |
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| Authors: | Tung-Ti Chang Mao-Feng Sun Kuan-Chung Chen Yung-Hao Wong Shun-Chieh Yang Hsin-Yi Chen |
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| Institution: | 1. Department of Chinese Pediatrics , China Medical University Hospital , Taichung, Taiwan ROC;2. Department of Acupuncture , China Medical University Hospital , Taichung, Taiwan ROC;3. Laboratory of Computational and Systems Biology , School of Chinese Medicine, China Medical University , Taichung, 40402, Taiwan ROC |
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| Abstract: | In search for novel anti-tumour agents targeting non-homologous end joining pathway, we conducted a virtual screening using traditional Chinese medicine (TCM) on Ku heterodimer which plays an important role on DNA break repair system. Docking results gave glycyrrhizic acid and macedonoside C as potential TCM candidates. Both glycyrrhizic acid and macedonoside C were docked onto the Ku heterodimer with high-predicted binding affinities as evidenced in their Dock Score. These two ligands also interact with key residues which have been previously shown to influence Ku DNA-binding affinity. Both compounds show consistent hydrogen bonding interactions with key residues throughout the 10- ns dynamics simulation run. Furthermore, glycyrrhizic acid and macedonoside C are able to form additional hydrogen bond interactions with positively charged Ku heterodimer surface. Such interactions strengthen the binding interaction of the top two TCM compounds with Ku heterodimer. Glycyrrhizic acid and macedonoside C are products of licorice (Glycyrrhiza glabra), which is a commonly used herb in TCM formulations. Overall, we report glycyrrhizic acid and macedonoside C as potential anti-tumour agents. |
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| Keywords: | traditional Chinese medicine docking DNA break repair system molecular dynamics anti-tumour |
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