• Title/Summary/Keyword: Systems biology

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Synthetic Bacteria for Therapeutics

  • Lam VO, Phuong N.;Lee, Hyang-Mi;Na, Dokyun
    • Journal of Microbiology and Biotechnology
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    • v.29 no.6
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    • pp.845-855
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    • 2019
  • Synthetic biology builds programmed biological systems for a wide range of purposes such as improving human health, remedying the environment, and boosting the production of valuable chemical substances. In recent years, the rapid development of synthetic biology has enabled synthetic bacterium-based diagnoses and therapeutics superior to traditional methodologies by engaging bacterial sensing of and response to environmental signals inherent in these complex biological systems. Biosynthetic systems have opened a new avenue of disease diagnosis and treatment. In this review, we introduce designed synthetic bacterial systems acting as living therapeutics in the diagnosis and treatment of several diseases. We also discuss the safety and robustness of genetically modified synthetic bacteria inside the human body.

Ligand Based Pharmacophore Identification and Molecular Docking Studies for Grb2 Inhibitors

  • Arulalapperumal, Venkatesh;Sakkiah, Sugunadevi;Thangapandian, Sundarapandian;Lee, Yun-O;Meganathan, Chandrasekaran;Hwang, Swan;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.33 no.5
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    • pp.1707-1714
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    • 2012
  • Grb2 is an adapter protein involved in the signal transduction and cell communication. The Grb2 is responsible for initiation of kinase signaling by Ras activation which leads to the modification in transcription. Ligand based pharmacophore approach was applied to built the suitable pharmacophore model for Grb2. The best pharmacophore model was selected based on the statistical values and then validated by Fischer's randomization method and test set. Hypo1 was selected as a best pharmacophore model based on its statistical values like high cost difference (182.22), lowest RMSD (1.273), and total cost (80.68). It contains four chemical features, one hydrogen bond acceptor (HBA), two hydrophobic (HY), and one ring aromatic (RA). Fischer's randomization results also shows that Hypo1 have a 95% significant level. The correlation coefficient of test set was 0.97 which was close to the training set value (0.94). Thus Hypo1 was used for virtual screening to find the potent inhibitors from various chemical databases. The screened compounds were filtered by Lipinski's rule of five, ADMET and subjected to molecular docking studies. Totally, 11 compounds were selected as a best potent leads from docking studies based on the consensus scoring function and critical interactions with the amino acids in Grb2 active site.

Inhibition of the Calcineurin Pathway by Two Flavonoids Isolated from Miliusa sinensis Finet & Gagnep.

  • Lee, Won Jeong;Moon, Jae Sun;Kim, Young Tae;Bach, Tran The;Hai, Do Van;Kim, Sung Uk
    • Journal of Microbiology and Biotechnology
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    • v.26 no.10
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    • pp.1696-1700
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    • 2016
  • In order to discover plant-derived signaling pathway inhibitors with antifungal properties, a two-component screening system utilizing the calcineurin and Hog1 mitogen-activated protein kinase pathways responsible for the virulence networks of Cryptococcus neoformans was employed, owing to the counter-regulatory actions of these pathways. Of the 1,000 plant extracts tested, two bioactive compounds from Miliusa sinensis were found to act specifically on the calcineurin pathway of C. neoformans. These compounds, identified as pashanone and 5-hydroxy-6,7-dimethoxyflavanone, exhibited potent antifungal activities against various human pathogenic fungi with minimum inhibitory concentration values ranging from 4.0 to >128 μg/ml.