ALL-ATOM MOLECULAR DYNAMICS SIMULATIONS OF S-ADENOSYL METHIONINE (SAM) ASSISTED

S-腺苷甲硫氨酸 (SAM) 辅助的全原子分子动力学模拟

• 批准号: 8364371
• 负责人: SHANTENU JHA
• 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/8364371
• 关键词: Affect; Binding; Biomedical Research; Elements; Funding; Genes; Grant; High Performance Computing; Messenger RNA; Methionine; Molecular; National Center for Research Resources; Pathway interactions; Principal Investigator; RNA; Research; Research Infrastructure; Resources; Role; Source; Structure; Time; United States National Institutes of Health; aptamer; cost; molecular dynamics

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 aim to investigate the complicated molecular mechanism of a SAM-I riboswitch RNA element with all-atom Molecular Dynamics (MD) simulations. The riboswitch RNA is a regulatory RNA element residing on 5'-untransrated region (UTR) of a target mRNA and regulate relevant genes in transcriptional or translational levels. Riboswitch RNAs are cis-acting regulatory RNA that comprises the aptamer domain and the expression domain. The complicated interplay between these two domains regulate a downstream gene in a mRNA, but the detailed molecular mechanisms remain elusive that are potentially affected by metabolite binding, roles of Mg2+, competing secondary structure elements, and dynamical distribution of secondary structures before binding a SAM. Therefore, examining the folded state stability as well as unfolding pathways with long time trajectories is beneficial for understanding molecular level information, which is further utilized to rationalize the molecular mechanism of the SAM-I riboswitch.

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。 我们的目的是研究复杂的分子机制的SAM-I核糖开关RNA元件与全原子分子动力学（MD）模拟。 核糖开关RNA（riboswitch RNA）是位于靶mRNA的5 ′-非翻译区（UTR）的调控RNA元件，在转录或翻译水平上调控相关基因。核糖开关RNA是包含适体结构域和表达结构域的顺式作用调节RNA。 这两个结构域之间复杂的相互作用调节mRNA中的下游基因，但详细的分子机制仍然难以捉摸，可能受到代谢物结合，Mg 2+的作用，竞争性二级结构元件和结合SAM之前二级结构的动态分布的影响。 因此，检查折叠状态的稳定性以及具有长时间轨迹的去折叠路径有利于理解分子水平的信息，其进一步用于使SAM-1核糖开关的分子机制合理化。