Classification and Characterization of RNA motifs

描述（由申请人提供）：本项目旨在开展与创建RNA本体的总体长期目标相关并支持其具体研究任务。在RNA学会的支持下，P.I.是RNA本体联盟（ROC）的先驱，该联盟汇集了感兴趣的科学家来开发RNA本体，该本体将整合有关RNA序列、二级和高分辨率3D结构以及RNA功能的各种数据，以便为生物医学界的用户创造更多关于RNA的可用知识。这些知识将采用完全集成的数据库的形式，包括序列比对和3D结构，以及更强大的软件，为实验室科学家带来先进的计算方法。它将促进和支持高度特异性和有效的基于rna的治疗方法的创造。RNA本体的一个主要组成部分将需要以结构化的方式写下所有在文献中提到或出现在数据库中的RNA基序的定义，并由RNA社区同意并由计算机解释。因此，本项目的具体目标包括：1)应用我们新的基于几何的RNA基序搜索程序“Find RNA 3D”（FR3D），在高分辨率RNA三维结构的非冗余数据库中搜索相似的发夹和内环基序。2)利用FR3D计算出的每对相似基序的差异评分，结合碱基配对注释等相关特征，对基序进行分类。3)识别家族内的共同结构特征，这些特征可以作为创建RNA基序系统分类（分类）的标准。这方面的工作将与中华民国的其他成员合作进行，以便就分类问题达成共识。4)应用FR3D识别新三维结构中非watson - crick碱基对的新例子，更新每个几何碱基对族的等构矩阵。使用FR3D，我们还可以执行特定于上下文的搜索。5)应用FR3D识别和分类高分辨率晶体结构中反复出现的等构基叠加模式。推导二核苷酸的经验基叠加倾向，并将这些数据与现有的热力学数据联系起来。6)应用FR3D识别结构相似的RNA三级相互作用，包括发夹或内部环与次要凹槽受体相互作用（“环-受体相互作用”）。

DESCRIPTION (provided by applicant): This project is designed to carry out specific research tasks relevant to and supportive of the overall, long- range goal of creating an RNA Ontology. The P.I. is spearheading the RNA Ontology Consortium (ROC), under the auspices of the RNA Society, which brings together interested scientists to develop an RNA Ontology that will integrate diverse data regarding RNA sequences, secondary and high-resolution 3D structures, and RNA function so as to create more usable knowledge about RNA for users in the biomedical community. This knowledge will take the form of fully integrated databases containing both sequence alignments and 3D structure and more powerful software to bring advanced computational methods to the bench scientist. It will facilitate and support the creation of highly specific and potent RNA-based therapeutics. A major component of the RNA Ontology will entail writing down definitions for all RNA motifs mentioned in the literature or appearing in databases, in a structured manner, agreed upon by the RNA community and interpretable by a computer. Thus, the specific aims of this project include: 1) To apply our new geometry-based RNA motif searching program, "Find RNA 3D" (FR3D), to search similar hairpin and internal loop motifs in the non-redundant database of high-resolution RNA 3D structures. 2) To use the discrepancy score calculated by FR3D for each pair of similar motifs, together with base-pairing annotations and other relevant features, to group motifs into families. 3) To identify common structural features within families that can serve as criteria for creating a systematic classification (taxonomy) of RNA motifs. This aspect of the work will be carried out in collaboration with other members of the ROC so as to achieve a consensus regarding classification issues. 4) To apply FR3D to identify new examples of non-Watson-Crick base-pairs in new 3D structures to update the Isostericity Matrices for each geometric base-pairing family. With FR3D we can also carry out context-specific searches. 5) To apply FR3D to identify and classify recurrent, isosteric base-stacking patterns in high-resolution crystal structures. To derive empirical base- stacking propensities for dinucleotides and to correlate these data with existing thermodynamic data. 6) To apply FR3D to identify structurally similar RNA tertiary interactions involving hairpin or internal loops interacting with minor groove receptors ("loop-receptor interactions").