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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们的目标是用全原子分子动力学(MD)模拟来研究SAM-I核糖开关RNA元件的复杂分子机制。核糖开关RNA是一种位于靶基因5‘-非转录区的调控元件，在转录或翻译水平上对相关基因进行调控。核糖开关RNA是由适配子结构域和表达结构域组成的顺式调控RNA。这两个结构域之间复杂的相互作用调节着mRNA中的下游基因，但详细的分子机制仍然不清楚，这些机制可能受到代谢物结合、镁离子的作用、竞争的二级结构元素以及与SAM结合之前二级结构的动态分布的影响。因此，考察SAM-I核糖开关的折叠状态稳定性以及长时间轨迹的展开路径有助于理解分子水平的信息，从而进一步合理地解释SAM-I核糖开关的分子机制。

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.