Folding RNA: From AIDS to the Human Genome

描述（由申请人提供）：本研究的最终目标是表征指导RNA折叠的相互作用，并使用此知识从其序列可靠地预测RNA分子的结构。 由于大多数疾病都是通过RNA介导的，而包括HIV在内的一些病毒具有RNA基因组，因此这些结果可以导致合理的治疗设计。 这些结果也将进一步解释人类基因组计划和其他测序工作所确定的序列。 这些结果也可能有助于打击生物恐怖主义，因为它们可能提供一种方法，一旦基因组被测序，就可以快速设计治疗方法。 寡核苷酸的热力学和结构性质的研究将为结构预测提供基础。 特别强调的是，将放在内部循环的稳定性和结构的序列依赖性。 通过自由能最小化进行二级结构预测将增加化学作图、序列比较和寡核苷酸结合的内容，以部分补偿影响折叠的因素的不完整知识。 将通过尝试确定反转录转座子的3'端的二级结构来测试该方法的功效。 也将追求的治疗设计的应用程序。

DESCRIPTION (provided by applicant): The ultimate goal of this research is to characterize the interactions directing RNA folding, and to use this knowledge to reliably predict structures of RNA molecules from their sequences. Since most diseases are mediated through RNA, and some viruses, including HIV, have RNA genomes, the results can lead to rational design of therapeutics. The results should also further the interpretation of sequences determined by the Human Genome Project and other sequencing efforts. The results may also contribute to fighting bioterrorism because they potentially provide a way to rapidly design therapeutics once a genome has been sequenced. The foundation for structure prediction will be provided by studies of the thermodynamic and structural properties of oligonucleotides. Particular emphasis will be placed on the sequence dependence of stability and structure for internal loops. Secondary structure prediction by free energy minimization will be augmented with constaints from chemical mapping, sequence comparison, and oligonucleotide binding to partially compensate for incomplete knowledge of the factors affecting folding. The power of the method will be tested by attempting to determine the secondary structure of the 3' end of a retrotransposon. Applications to design of therapeutics will also be pursued.