RNA DYNAMICS: FROM GLOBAL STRUCTURE TO ATOMIC DETAIL

RNA 动力学：从整体结构到原子细节

基本信息

批准号：
8656881
负责人：
Ron Elber
金额：
$ 35.17万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8656881
关键词：
Adopted Agreement Antibiotic Resistance Antibiotics Awareness Bacteria Bacterial RNA Behavior Binding Binding Sites Biological Biological Process Catalytic RNA Cells Charge Collaborations Coupled Coupling DNA Sequence DNA Sequence Rearrangement Drug Design Drug Targeting Environment Equilibrium Event Excision Free Energy Funding Genes Genetic Genetic Code Genome Glean Goals Hydration status Instruction Ions Kinetics Link Measures Mediating Messenger RNA Methods Modeling Molecular Molecular Conformation Molecular Machines Motion Nature Nucleotides Pathway interactions Pharmaceutical Preparations Process RNA RNA Binding RNA Folding RNA Sequences Reaction Relative (related person)Research Ribosomes Role Sampling Secretory Component Shapes Site Small RNA Spatial Distribution Spliced Genes Structure System Techniques Testing Tetrahymena Time Validation Vertebral column Vision Work base drug development innovation inorganic phosphate insight millisecond molecular dynamics mutant public health relevance research study simulation small molecule tool

项目摘要

DESCRIPTION (provided by applicant): RNA is a molecular machine that carries out a large number of tasks within the cell. The awareness of its central involvement in biological processes is among the most remarkable scientific discoveries of the last thirty years. In the earliest models, RNA's role was relegated to that of messenger, passively copying and transporting pieces of the genetic code. Recent research illustrates its active participation in executing the instructions present in the genome. RNA's widely-varying functions range from 'splicing' genes together to regulating the concentrations of key metabolites. Many of these newly discovered roles rely on RNA folding to specific functional structures and responding to the environment by dynamically changing shape. The goal of this proposal is to obtain an atomically detailed picture of the RNA folding process. This vision is beyond current experimental capabilities, but is on the horizon for new simulation methods. However, simulation must be validated by observation. This project identifies important landmarks along the folding pathway of a small RNA that can be detected with advanced experimental tools. Observation of the time scale for and sequences of events will be determined by experiment, and used to validate simulations, which provide insight into atomically detailed processes. The expanding appreciation of RNA's biological roles brings recognition of its potential as a new target for drugs. Insights gained int the atomic level workings of RNA folding and dynamics may assist with RNA based drug design.

描述（由申请人提供）：RNA是一种分子机器，在细胞内执行大量任务。认识到其在生物过程中的核心作用是过去三十年来最引人注目的科学发现之一。在最早的模型中，RNA 的作用被降级为信使，被动地复制和运输遗传密码的片段。最近的研究表明它积极参与执行基因组中存在的指令。 RNA 的功能多种多样，从“剪接”基因到调节关键代谢物的浓度。许多新发现的作用都依赖于 RNA 折叠成特定的功能结构，并通过动态改变形状来响应环境。该提案的目标是获得 RNA 折叠过程的原子详细图像。这一愿景超出了当前的实验能力，但即将出现新的模拟方法。然而，模拟必须通过观察来验证。该项目确定了小 RNA 折叠路径上的重要标志，可以使用先进的实验工具进行检测。对事件的时间尺度和顺序的观察将通过实验确定，并用于验证模拟，从而提供对原子详细过程的洞察。人们对 RNA 生物学作用的认识不断加深，人们认识到它作为新药物靶点的潜力。在 RNA 折叠和动力学的原子水平工作中获得的见解可能有助于基于 RNA 的药物设计。