完整的RNA反向折叠：功能性锤头状核酶的计算设计
Complete RNA inverse folding: computational design of functional hammerhead ribozymes
摘要：
纳米技术和合成生物学目前构成了最具创新性的跨学科研究领域之一，有望从根本上改变21世纪的社会。本文涉及核糖核酸分子的合成设计，使用我们最近的算法，RNAiFold，它可以确定所有的RNA序列，其最小自由能二级结构是用户指定的目标结构。使用RNAiFold，我们设计了10个顺式切割锤头核酶，所有这些都通过切割测定显示出功能。我们还使用RNAiFold来设计功能性顺式切割锤头，作为合成的较大RNA的模块化单元。对这一小部分锤头的动力学分析表明，计算设计的核酶的切割速率可能与位置熵、系综缺陷、结构柔性/刚性和相关措施相关。人工核酶在过去已经被手动或通过SELEX（指数富集配体的系统进化）设计;然而，这似乎是第一个纯计算设计和实验验证的新型功能性核酶。RNAiFold可在http://bioinformatics.bc.edu/clotelab/RNAiFold/上获得。
英文摘要：
Nanotechnology and synthetic biology currently constitute one of the most innovative, interdisciplinary fields of research, poised to radically transform society in the 21st century. This paper concerns the synthetic design of ribonucleic acid molecules, using our recent algorithm, RNAiFold, which can determine all RNA sequences whose minimum free energy secondary structure is a user-specified target structure. Using RNAiFold, we design ten cis-cleaving hammerhead ribozymes, all of which are shown to be functional by a cleavage assay. We additionally use RNAiFold to design a functional cis-cleaving hammerhead as a modular unit of a synthetic larger RNA. Analysis of kinetics on this small set of hammerheads suggests that cleavage rate of computationally designed ribozymes may be correlated with positional entropy, ensemble defect, structural flexibility/rigidity and related measures. Artificial ribozymes have been designed in the past either manually or by SELEX (Systematic Evolution of Ligands by Exponential Enrichment); however, this appears to be the first purely computational design and experimental validation of novel functional ribozymes. RNAiFold is available at http://bioinformatics.bc.edu/clotelab/RNAiFold/.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
