Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Howrah, India.
Department of Chemistry, Bose Institute, Kolkata, India.
PLoS One. 2020 Feb 13;15(2):e0228967. doi: 10.1371/journal.pone.0228967. eCollection 2020.
The DevRS two-component system plays a pivotal role in signal transmission and downstream gene regulation in Mycobacterium tuberculosis. Under the hypoxic condition, phosphorylated DevR interacts with multiple binding sites at the promoter region of the target genes. In the present work, we carried out a detailed computational analysis to figure out the sensitivity of the kinetic parameters. The set of kinetic parameters takes care of the interaction among phosphorylated DevR and the binding sites, transcription and translation processes. We employ the method of stochastic optimization to quantitate the relevant kinetic parameter set necessary for DevR regulated gene expression. Measures of different correlation coefficients provide the relative ordering of kinetic parameters involved in gene regulation. Results obtained from correlation coefficients are further corroborated by sensitivity amplification.
DevRS 双组份系统在结核分枝杆菌信号转导和下游基因调控中起着关键作用。在低氧条件下，磷酸化的 DevR 与靶基因启动子区域的多个结合位点相互作用。在本工作中，我们进行了详细的计算分析，以确定动力学参数的灵敏度。这组动力学参数考虑了磷酸化 DevR 与结合位点、转录和翻译过程之间的相互作用。我们采用随机优化方法来量化调控基因表达所需的相关动力学参数集。不同相关系数的度量为参与基因调控的动力学参数提供了相对顺序。相关系数得到的结果进一步通过灵敏度放大得到证实。
