REFINE RNA BACKBONE AND REMOVE STERIC CLASHES BY GEOMETRIC ALGORITHMS

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。 RNA结构中准确的细节对于理解RNA的功能很重要，但骨架构象很难确定，而且大多数现有的RNA结构都显示出严重的空间碰撞。在细胞信号转导中，核糖开关等小RNA分子经常与配体相互作用，从而引发基因表达等细胞基本活动的改变，这些RNA-配体相互作用往往涉及特定的骨架相互作用，而RNA骨架的细节对于理解相互作用机制是至关重要的。在我们之前的工作中，我们开发了一个名为RNABC(RNA Backbone校正)的程序，该程序可以在二核苷酸中搜索具有可接受几何形状的替代无冲突构象。RNABC的结果是可以接受的，但要成为一个成熟的工具还有很长的路要走。我们计划使用各种几何技术来提高RNABC的可解性和速度，分析RNA的理论模型和实验数据，推导几何规则以更好地理解RNA几何，并开发3D交互程序，供结晶学家和其他研究人员优化RNA结构。 具体目标是： 1.改进了现有RNABC程序的可解性和效率，该程序为RNA二核苷酸骨架提供了无冲突的替代构象，并对RNABC进行了扩展，为多核苷酸提供了无冲突的替代构象。 2.分析了理论空间填充模型和实验结晶学数据中RNA骨架二面角和RNA骨架构象的分布，得出了有助于理解RNA结构和整合到RNABC中的几何规则。 3.开发了基于RNABC的3D交互程序，作为核酸结晶学家和其他研究人员精炼RNA结构的图形用户界面。

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. Accurate details in RNA structures are important for understanding RNA function, but the backbone conformation is difficult to determine and most existing RNA structures show serious steric clashes. In cell signaling, small RNA molecules such as riboswitches often interact with ligands to trigger changes of basic cellular activities such as gene expressions, where these RNA-ligand interactions often involve specific backbone interactions and the details of RNA backbones are essential for understanding the interaction mechanisms. In our previous work, we have developed a program called RNABC (RNA Backbone Correction) that searches for alternative clash-free conformations with acceptable geometry in a dinucleotide. The results from RNABC are acceptable but it still has a long way to become a mature tool. We plan to use various geometric techniques to improve RNABC in both solvability and speed, analyze RNA both theoretical model and experimental data and derive geometric rules to better understand RNA geometry, and develop 3D interactive program for crystallographers and other researchers to refine RNA structures. The specific aims are: 1. Improving solvability and efficiency of current RNABC (RNA Backbone Correction) program, which provides clash-free alternative conformations for RNA dinucleotide backbone, and expanding RNABC to provide clash-free alternative conformations for multi-nucleotides. 2. Analyzing distributions of RNA backbone dihedral angles and RNA backbone conformations in theoretical space-filling model and experimental crystallographic data and deriving geometric rules to help understand RNA structures and incorporate into RNABC. 3. Developing 3D interactive program based on RNABC as a graphical user interface for nucleic acid crystallographers and other researchers to refine RNA structures.