DETERMINING THE FOLDING PATHWAYS OF RNA USING LARGE-SCALE OPTIMIZATION

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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 大的生物聚合物（如蛋白质和RNA）折叠成复杂的三维结构，在细胞中执行高度特异性的功能。折叠过程通常是调节性的，因为只有正确的结构才能发挥功能。折叠（或组装）的核心是驱动反应的基本物理原理。我们模拟这些系统的能力受到生物相关分子非常大的尺寸和复杂性的限制。我们已经开发了一种算法（KinFold，在Laederach等人，J Mol Biol，358，1179-1190），其基于时间分辨足迹实验确定了溶剂可及性测量的最佳拟合动力学模型。该方法详尽列举了所有可能的动力学模型拓扑结构，并确定最佳拟合模型拓扑结构。我们现在已经收集了一系列的7个实验，在这些实验中，我们在不同的温度下折叠了一个大的RNA，以确定热力学激活参数。这些数据将需要对每个实验条件测试84个模型拓扑结构。每次优化都需要英特尔处理器上50小时的CPU。因此，我想在SDSC的IA 64集群上请求7 x84 x50 = 29400 CPU小时。 开始日期 2007年03月14日00：00：00

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. Large biopolymers (such as proteins and RNA) fold into complex three-dimensional structures that carry out highly specific functions in the cell. The folding process is often regulatory, as only the correct structure carries out function. At the heart of folding (or assembly) are basic physical principles that drive the reaction. Our ability to model these systems is limited by the very large size and complexity of biologically relevant molecules. We have developed an algorithm (KinFold, described in Laederach et al., J Mol Biol, 358, 1179-1190) that identifies the best fitting kinetic models to measures of solvent accessibility based on time-resolved footprinting experiments. The approach exhaustively enumerates all possible kinetic model topologies and identifies the best fitting model topology. We have now collected a series of 7 experiments in which we have folded a large RNA at different temperatures to determine the thermodynamic activation parameters. This data will require testing 84 model topologies for each experimental condition. Each optimization requires 50 hours of CPU on an Intel processor. I would therefore like to request 7x84x50= 29400 CPU hours on the IA 64 cluster at SDSC. Start Date 03/14/2007 00:00:00