A MESOSCOPIC LATTICE MODEL FOR STUDYING NUCLEIC ACID FOLDING DYNAMICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 核糖核酸(RNA)在重要的细胞过程中发挥着重要作用，如转录和翻译。目前，大多数RNA链的折叠机制和途径还没有完全阐明。利用我们的蒙特卡罗晶格模型，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。大多数目前的模型几乎没有提供对导致在自然界中观察到的不同RNA三级结构的折叠过程的洞察。我们假设，有洞察力的机械模型应该保留与序列相关的信息，在纳秒到毫秒的时间尺度上适合折叠。尽管原子论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，细棒模型可以处理超过1000个核苷酸的链，但丢弃了特定于序列的细节，并被限制在毫秒量级的最小时间尺度上。我们的目标是建立一个粗粒度的介观模型，在离散的空间中结合序列效应。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，平衡一个溶剂化的三核苷酸长的玩具结构需要25天。在TeraGrid上使用200000 SU启动分配将允许我们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。

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.