DETERMINING THE FOLDING PATHWAYS OF RNA USING LARGE-SCALE OPTIMIZATION

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。 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定的功能。折叠过程通常是有调节的，因为只有正确的结构才能发挥作用。折叠(或组装)的核心是驱动反应的基本物理原理。我们对这些系统进行建模的能力受到生物相关分子的巨大尺寸和复杂性的限制。我们开发了一种算法(KinFold，在Laederach等人，J Mol Biol，358,1179-1190中描述)，该算法基于时间分辨足迹实验确定最佳拟合动力学模型来衡量溶剂可及性。该方法详尽地列举了所有可能的动力学模型拓扑，并确定了最适合的模型拓扑。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来确定热力学激活参数。这些数据将需要为每个实验条件测试84个模型拓扑。每次优化都需要在英特尔处理器上运行50小时的CPU。因此，我想在国资委的IA集群上请求7x84x50=29400个CPU小时。 开始日期2007-03-14 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