A MESOSCOPIC LATTICE MODEL FOR STUDYING NUCLEIC ACID FOLDING DYNAMICS

用于研究核酸折叠动力学的介观晶格模型

• 批准号: 8171900
• 负责人: LUIS A. Nunes AMARAL
• 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/8171900
• 关键词: Biophysics; Cell physiology; Cereals; Computer Retrieval of Information on Scientific Projects Database; Freedom; Funding; Genetic Transcription; Grant; Hand; Illinois; Institution; Laboratories; Lead; Modeling; Nature; Nucleic Acid Folding; Nucleotides; Pathway interactions; Play; Process; RNA; Research; Research Personnel; Resolution; Resources; Role; Simulate; Source; Structure; Study models; Time; Toy; Translations; United States National Institutes of Health; Universities; insight; millisecond; molecular dynamics; nanosecond; retinal rods; software development

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. Ribonucleic acids (RNA) play an essential role in vital cell processes such as transcription and translation. At present, the folding mechanisms and pathways of most RNA strands have not been fully elucidated. With our Monte Carlo lattice model, we aim to predict the folded structure of RNA strands less than 100 nucleotides long and to study their folding dynamics. Most current models offer little insight into the folding processes that lead to the varied RNA tertiary structures observed in nature. We postulate that insightful mechanistic models should retain sequence-specific information relevant over the nanosecond to millisecond time-scales appropriate for folding. Although atomistic models offer a high resolution, simulating a ten nucleotide strand for longer than ten nanoseconds is computationally intractable. Thin rod models on the other hand, can handle strands longer than 1000 nucleotides, but discard sequence-specific details and are limited to a minimum time-scale on the order of milliseconds. We aim to build a coarse grained, mesoscopic model that incorporates sequence effects in a discretized space. We will use molecular dynamics simulations to find the degrees of freedom relevant to our time-scale. We are using NAMD 2.6, a software developed by the Theoretical and Computational Biophysics Group at the University of Illinois at Urbana-Champaign. On a single node in our laboratory, equilibrating a solvated three nucleotide-long toy structure takes 25 days. Using the 200000 SUs start up allocation on Teragrid will allow us to simulate a more relevant ten nucleotide strand and enable us to validate our model.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 核糖核酸 (RNA) 在转录和翻译等重要细胞过程中发挥着重要作用。目前，大多数RNA链的折叠机制和途径尚未完全阐明。通过我们的蒙特卡罗格子模型，我们的目标是预测长度小于 100 个核苷酸的 RNA 链的折叠结构并研究它们的折叠动力学。目前大多数模型对导致自然界中观察到的各种 RNA 三级结构的折叠过程几乎没有提供深入的了解。我们假设有洞察力的机制模型应该保留适合折叠的纳秒到毫秒时间尺度内的序列特异性信息。尽管原子模型提供了高分辨率，但模拟十个核苷酸链超过十纳秒在计算上是困难的。另一方面，细杆模型可以处理超过 1000 个核苷酸的链，但会丢弃序列特定的细节，并且仅限于毫秒量级的最小时间尺度。我们的目标是建立一个粗粒度的介观模型，将序列效应纳入离散空间中。我们将使用分子动力学模拟来找到与我们的时间尺度相关的自由度。我们使用的是 NAMD 2.6，这是由伊利诺伊大学厄巴纳-香槟分校理论和计算生物物理学小组开发的软件。在我们实验室的单个节点上，平衡溶剂化的三核苷酸长玩具结构需要 25 天。使用 Teragrid 上的 200000 个 SU 启动分配将使我们能够模拟更相关的十个核苷酸链，并使我们能够验证我们的模型。