Computational Methods for Tertiary RNA Folding and Novel RNA Design

RNA 三级折叠和新型 RNA 设计的计算方法

基本信息

批准号：
0727001
负责人：
Tamar Schlick
金额：
$ 40万
依托单位：
New York University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2013-09-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=0727001&HistoricalAwards=false
关键词：
Computational Methods Tertiary RNA Folding

项目摘要

Project Abstract (NSF 0727001)Computational Methods for Tertiary RNA Folding and Novel RNA DesignRecent discoveries have revealed RNA's wonderful capacity to form complex three-dimensional structures, as well as perform many molecular functions beyond storage of biological information. RNA's newly realized powers are being exploited in bioengineering and nanotechnology for design and application of biological sensors for detecting chemical compounds (for example, toxins), RNA enzymes for enabling faster chemical reactions, RNA switches for controlling protein synthesis in the cell, and RNA microarrays for monitoring gene expression. These advances in RNA science have relied mostly on experimental techniques (for example, X-ray crystallography). However, the systematic theoretical 3D structure determination and design approaches that have greatly benefited protein science are largely lacking for RNA. This void hampers the integration of experimental and theoretical tools required for advancing emerging RNA applications in bioengineering and nanotechnology. This research focuses on developing computational technologies for RNA 3D structure prediction and design. For RNA 3D structure prediction, the investigators study algorithmic development issues involving calculating and testing RNA statistical potentials, and developing/applying effective Monte Carlo conformational sampling algorithms coupled with the fragment assembly approach, a successful method for protein structure prediction. In particular, the investigators examine the role of multibody interactions in RNA 3D structure prediction. For RNA 3D design, the investigators focus on procedures for designing novel RNAs with tailored functions by a systematic computational approach. This work involves integrating RNA 2D/3D folding algorithms with advanced dynamics analysis tools (for example, QM/MM, transition path sampling) to screen and elucidate the structural, dynamical, and ligand-binding properties of designed RNAs. The computational tools for RNA 3D structure prediction and design resulting from the studies are being made available as a software package to the research community.

项目摘要 (NSF 0727001)RNA 三级折叠和新型 RNA 设计的计算方法最近的发现揭示了 RNA 形成复杂三维结构的奇妙能力，以及执行除生物信息存储之外的许多分子功能的能力。 RNA 新实现的能力正在生物工程和纳米技术中被利用，用于设计和应用用于检测化合物（例如毒素）的生物传感器、用于实现更快化学反应的 RNA 酶、用于控制细胞中蛋白质合成的 RNA 开关以及 RNA 微阵列用于监测基因表达。 RNA 科学的这些进步主要依赖于实验技术（例如 X 射线晶体学）。然而，RNA 很大程度上缺乏使蛋白质科学受益匪浅的系统理论 3D 结构测定和设计方法。这一空白阻碍了推进生物工程和纳米技术中新兴 RNA 应用所需的实验和理论工具的整合。本研究重点开发用于 RNA 3D 结构预测和设计的计算技术。对于 RNA 3D 结构预测，研究人员研究了算法开发问题，包括计算和测试 RNA 统计势，以及开发/应用有效的蒙特卡罗构象采样算法以及片段组装方法（一种成功的蛋白质结构预测方法）。研究人员特别研究了多体相互作用在 RNA 3D 结构预测中的作用。对于 RNA 3D 设计，研究人员重点关注通过系统计算方法设计具有定制功能的新型 RNA 的程序。这项工作涉及将 RNA 2D/3D 折叠算法与先进的动力学分析工具（例如 QM/MM、转换路径采样）相集成，以筛选和阐明设计的 RNA 的结构、动力学和配体结合特性。研究产生的 RNA 3D 结构预测和设计的计算工具正在作为软件包提供给研究界。