Next-generation computational/chemical methods for complex RNA structures
用于复杂 RNA 结构的下一代计算/化学方法
基本信息
- 批准号:10393151
- 负责人:
- 金额:$ 0.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAdoptionAnti-Bacterial AgentsAntiviral AgentsBacteriaBehaviorBiochemicalBiologicalBiomedical EngineeringBiomedical ResearchBiophysicsChemicalsCommunitiesComplexCryoelectron MicroscopyCrystallographyDevelopmentDiseaseEngineeringHIVHeterogeneityLifeMedicalMethodsModificationMolecular ConformationMutationOrganismPhylogenetic AnalysisPlayProteinsRNARNA FoldingRegulationResearchRetroviridaeRoleSavingsSoftware ToolsStructureTechnologyTestingUntranslated RNAViralWorkbiochemical toolsblindcomputerized toolsdesignexperimental studygenetic informationmodel designmolecular modelingneoplastic cellnext generationnovelprospectivestructural biologysuccesstargeted treatmenttherapeutic genome editingthree dimensional structuretool
项目摘要
PROJECT SUMMARY
The continuing discoveries of non-coding RNAs and their critical roles in cellular and
viral machinery are inspiring novel antibacterial, antitumor, antiviral, and genome-editing
therapies based on disabling, manipulating, and repurposing the RNAs involved.
Unfortunately, our poor biophysical understanding of `how RNAs work' hinders the
development of these potentially life-saving efforts. A critical bottleneck has been the
inapplicability of crystallography, NMR, cryoelectron microscopy, phylogenetic analysis,
and biochemical methods to determine the partly ordered conformations of non-coding
RNAs in all their functional states. To resolve this bottleneck, we are developing
experimental methods and complementary computational approaches that give rich
information sufficient to infer and engineer RNA secondary and tertiary structures and
their heterogeneous ensembles, evaluated through community-wide blind trials,
prospective compensatory mutation/rescue experiments, and global RNA design
challenges. Here, we outline expansions of our research that will rigorously address four
biomedically significant problems that have so far seen limited progress in molecular
modeling efforts: the heterogeneity of RNA structures within their native cellular and viral
contexts; modeling and design of RNA's biological interactions with proteins and other
molecules, modulated by chemical modification; high-accuracy calculation of RNA
folding energetics; and the automated design of dynamic 3D RNA structures for eventual
medical applications. We will evaluate success through continuing blind trials,
independent tests by more than a dozen expert biological and bioengineering
collaborators, and through adoption of our methods and software tools by the broader
research community. In the same way that specialized structural biology tools and
computational design are establishing a firm understanding of protein behavior and
regulation, we propose that the technologies outlined here will transform our
understanding of structure in non-coding RNAs, providing a stronger basis for their
biomedical activation or disruption.
项目摘要
非编码RNA的不断发现及其在细胞和生物学中的关键作用
病毒机制正在激发新的抗菌,抗肿瘤,抗病毒和基因组编辑
基于禁用,操纵和重新利用相关RNA的疗法。
不幸的是,我们对“RNA如何工作”的生物物理学理解不足,阻碍了对RNA的研究。
这些潜在的拯救生命的努力。一个关键的瓶颈是,
晶体学、核磁共振、低温电子显微镜、系统发育分析
和生物化学方法来确定非编码的部分有序构象
所有功能状态的RNA。为了解决这个瓶颈,我们正在开发
实验方法和互补的计算方法,
足以推断和工程化RNA二级和三级结构的信息,
他们的异质性集合,通过社区范围内的盲法试验进行评估,
前瞻性补偿突变/拯救实验和全局RNA设计
挑战在这里,我们概述了我们的研究,将严格解决四个扩展
生物医学上的重大问题,迄今为止,在分子生物学上的进展有限,
建模工作:RNA结构在其天然细胞和病毒中的异质性
RNA与蛋白质和其他生物相互作用的建模和设计
分子,通过化学修饰进行调节; RNA的高精度计算
折叠能量学;以及动态3D RNA结构的自动化设计,
医疗应用。我们将通过持续的盲法试验来评估成功与否,
由十多位生物和生物工程专家进行的独立测试
合作者,并通过采用我们的方法和软件工具,由更广泛的
研究社区。就像专门的结构生物学工具和
计算机设计正在建立对蛋白质行为的坚定理解,
监管,我们建议,这里概述的技术将改变我们的
了解非编码RNA的结构,为他们的研究提供更强的基础。
生物医学激活或破坏。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rhiju Das其他文献
Rhiju Das的其他文献
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{{ truncateString('Rhiju Das', 18)}}的其他基金
Modeling and design of complex RNA structures
复杂 RNA 结构的建模和设计
- 批准号:
10685534 - 财政年份:2017
- 资助金额:
$ 0.74万 - 项目类别:
Next-generation computational/chemical methods for complex RNA structures
用于复杂 RNA 结构的下一代计算/化学方法
- 批准号:
9765345 - 财政年份:2017
- 资助金额:
$ 0.74万 - 项目类别:
Modeling and design of complex RNA structures
复杂 RNA 结构的建模和设计
- 批准号:
10405315 - 财政年份:2017
- 资助金额:
$ 0.74万 - 项目类别:
Next-generation computational/chemical methods for complex RNA structures
用于复杂 RNA 结构的下一代计算/化学方法
- 批准号:
9277079 - 财政年份:2017
- 资助金额:
$ 0.74万 - 项目类别:
Next-generation computational/chemical methods for complex RNA structures
用于复杂 RNA 结构的下一代计算/化学方法
- 批准号:
10220066 - 财政年份:2017
- 资助金额:
$ 0.74万 - 项目类别:
Non-coding RNA Structure through a Mutate-and-Map Strategy
通过突变和映射策略研究非编码 RNA 结构
- 批准号:
8899593 - 财政年份:2012
- 资助金额:
$ 0.74万 - 项目类别:
Internet-scale discovery of RNA bioengineering rules
互联网规模发现RNA生物工程规则
- 批准号:
8274073 - 财政年份:2012
- 资助金额:
$ 0.74万 - 项目类别:
Non-coding RNA Structure through a Mutate-and-Map Strategy
通过突变和映射策略研究非编码 RNA 结构
- 批准号:
8345532 - 财政年份:2012
- 资助金额:
$ 0.74万 - 项目类别:
Correcting Pervasive Errors in RNA Crystallography with Rosetta
使用 Rosetta 纠正 RNA 晶体学中普遍存在的错误
- 批准号:
8355778 - 财政年份:2012
- 资助金额:
$ 0.74万 - 项目类别:
Internet-scale discovery of RNA bioengineering rules
互联网规模发现RNA生物工程规则
- 批准号:
8668102 - 财政年份:2012
- 资助金额:
$ 0.74万 - 项目类别:
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