REFINE RNA BACKBONE AND REMOVE STERIC CLASHES BY GEOMETRIC ALGORITHMS

这个子项目是众多研究子项目之一

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.