RNA DYNAMICS: FROM GLOBAL STRUCTURE TO ATOMIC DETAIL

描述（由申请人提供）：RNA是一种在细胞内执行大量任务的分子机器。意识到它在生物过程中的核心作用是近三十年来最显著的科学发现之一。在最早的模型中，RNA的角色被降级为信使，被动地复制和运输遗传密码片段。最近的研究表明，它积极参与执行基因组中存在的指令。RNA的功能千变万化，从“剪接”基因到调节关键代谢物的浓度。许多这些新发现的作用依赖于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。这项提议的目标是获得RNA折叠过程的原子细节图。这一愿景超出了目前的实验能力，但新的模拟方法即将出现。然而，模拟必须通过观察来验证。该项目确定了沿着小RNA折叠途径的重要里程碑，可以用先进的实验工具检测到。对事件的时间尺度和序列的观察将由实验确定，并用于验证模拟，这提供了对原子细节过程的洞察。对RNA生物学作用的进一步认识使人们认识到它作为药物新靶点的潜力。在RNA折叠和动力学的原子水平上获得的见解可能有助于基于RNA的药物设计。

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.