ORIGIN OF FRICTION IN THE FOLDING RATES OF RNA HAIRPINS

RNA 发夹折叠速率中的摩擦起源

• 批准号: 8171862
• 负责人: Samuel Cho
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171862
• 关键词: Affect; Amber; Cell physiology; Cells; Chloride Ion; Chlorides; Computer Retrieval of Information on Scientific Projects Database; DNA; Friction; Funding; Gene Expression; Genetic Transcription; Grant; Institution; Names; Proteins; RNA; RNA Splicing; RNA Stability; Reaction; Research; Research Personnel; Resources; Running; Source; Structure; Sugar Phosphates; Testing; United States National Institutes of Health; Urea; Vertebral column; base; programs; research study; ribose phosphate; simulation; trimethyloxamine

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Biomolecules in the cell interact with numerous partners, including small organic molecules called osmolytes that affect their stability. Some well-known osmolytes such as urea and guandinium chloride are known to destabilize proteins, RNA, and DNA molecules, but TMAO has notably demonstrated to stabilize proteins. The effects of TMAO on RNA molecules have not been thoroughly explored even though changes in stabilities of RNA molecules can profoundly affect a number of cellular functions that include gene expression, transcription, and splicing reactions, just to name a few. Recent experimental studies by Lamber and Draper (JMB, 2007) showed that the secondary structures of RNA are destabilized but the tertiary interactions are stabilized by TMAO. They hypothesized that the destabilization of the secondary structures is a result of preferential accumulation of osolytes around base groups and depletion around the ribose-phosphate backbone. In our present proposed study, we plan on studying the effect of TMAO interactions with RNA hairpins to microscopically test the hypotheses put forth by Lambert and Draper's study. Specifically, we will use all-atom MD simulations using the CHARMM and AMBER force fields to determine the preferred interactions of TMAO with the specific base, sugar, and phosphate moieties of RNA. We will use the NAMD MD program to run our simulations because a) it has been demonstrated to scale well will parallelization and b) it can support both the CHARMM and AMBER force fields making a direct comparison possible.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞中的生物分子与许多伙伴相互作用，包括影响其稳定性的称为渗透剂的小有机分子。一些众所周知的渗透剂，如尿素和氯化胍，已知会使蛋白质、RNA和DNA分子不稳定，但TMAO已明显证明能稳定蛋白质。TMAO对RNA分子的影响尚未得到彻底研究，尽管RNA分子稳定性的变化可以深刻影响许多细胞功能，包括基因表达，转录和剪接反应，仅举几例。Lamber和德雷珀（JMB，2007）最近的实验研究表明，RNA的二级结构是不稳定的，但三级相互作用是稳定的TMAO。他们假设二级结构的不稳定是碱基周围的渗透细胞优先积累和核糖磷酸骨架周围消耗的结果。在我们目前提出的研究中，我们计划研究TMAO与RNA发夹相互作用的影响，以微观上测试Lambert和德雷珀的研究提出的假设。具体来说，我们将使用全原子MD模拟使用CHARMM和琥珀力场，以确定TMAO与RNA的特定碱基，糖和磷酸部分的优选相互作用。我们将使用NAMD MD程序来运行我们的模拟，因为a）它已被证明可以很好地扩展并行化，B）它可以支持CHARMM和AMBER力场，从而可以进行直接比较。