CHARACTERIZATION OF DYNAMICS CONTROL OF CHEMOTAXIS INITIATION

趋化引发的动力学控制特征

• 批准号: 8364355
• 负责人: JEROME BAUDRY
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364355
• 关键词: Biomedical Research; Cells; Chemicals; Chemotaxis; Complex; Escherichia coli; Funding; Grant; High Performance Computing; Modification; Mutation; National Center for Research Resources; Phosphotransferases; Principal Investigator; Protein Dynamics; Proteins; Research; Research Infrastructure; Resources; Signal Transduction; Signaling Protein; Simulate; Source; Time; Translating; United States National Institutes of Health; Variant; cost; extracellular; in vivo; molecular dynamics; protein structure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We will perform three independent 15 microseconds molecular dynamics simulations (45 microseconds total) of E. coli's chemotaxis signaling protein that translates extracellular signals into the cell and activates kinase complexes. Known mutations (equivalent to in vivo chemical modifications) can suppress ('locked-off') or hyper-activate ('locked-on') the wild-type protein's basal kinase activation. The accepted, but unproven, functional hypothesis is that mutations modify the protein's structure and dynamics. We will simulate the wild-type, locked-on (hyperactive) and locked-off (inactive) species for 15 microseconds each to characterize for the first time how variations in protein structure and dynamics control the initiation of the chemotactic signal.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们将进行三个独立的15微秒分子动力学模拟（共45微秒）的E。大肠杆菌的趋化性信号蛋白，将细胞外信号翻译到细胞内并激活激酶复合物。已知的突变（相当于体内化学修饰）可以抑制（“锁定”）或过度激活（“锁定”）野生型蛋白的基础激酶激活。公认但未经证实的功能假说是突变改变了蛋白质的结构和动力学。我们将模拟野生型，锁定（过度活跃）和锁定（非活性）物种各15微秒，以首次表征蛋白质结构和动力学的变化如何控制趋化信号的启动。