A MESOSCOPIC LATTICE MODEL FOR STUDYING NUCLEIC ACID FOLDING DYNAMICS

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。 核糖核酸（RNA）在转录和翻译等重要细胞过程中起着重要作用。目前，大多数RNA链的折叠机制和途径尚未完全阐明。我们的Monte Carlo晶格模型，我们的目标是预测折叠结构的RNA链小于100个核苷酸长，并研究其折叠动力学。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任何见解。我们假设，有见地的机械模型应该保留序列特定的信息相关的纳秒到毫秒的时间尺度适合折叠。虽然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，细杆模型可以处理长于1000个核苷酸的链，但丢弃序列特异性细节，并且限于毫秒级的最小时间尺度。我们的目标是建立一个粗粒度，介观模型，在离散空间中的序列效应。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厄巴纳-香槟分校的理论和计算生物物理学小组开发的软件。在我们实验室的一个节点上，平衡一个溶剂化的三个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.