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，并利用这些知识从RNA分子的序列中可靠地预测其结构。由于大多数疾病是通过RNA介导的，而包括艾滋病毒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设计治疗方法。该结果也将进一步解释由人类基因组计划和其他测序工作确定的序列。这些结果也可能有助于打击生物恐怖主义，因为一旦基因组测序完成，它们可能提供一种快速设计治疗方法的方法。

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.