High-resolution modeling of protein-RNA interfaces
蛋白质-RNA 界面的高分辨率建模
基本信息
- 批准号:10641354
- 负责人:
- 金额:$ 11.4万
- 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:2017-09-15 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
SUMMARY
RNA-protein interactions mediate multiple critical regulatory steps in the translation of information from the
genome to the cellular machine, and corruptions of these fundamental interactions are implicated throughout
infectious and inherited disease, neurodegeneration, and cancer. Unfortunately, a scarcity of predictive
computational tools for RNA-protein interactions is slowing the development of potentially life-saving efforts
that either target or repurpose these interactions to address human disease. This proposal brings together four
labs to resolve this bottleneck, building on our recent studies that have achieved – all for the first time – blind
protein-RNA structure predictions reaching near-atomic resolution, large-scale prediction of protein-RNA
binding energetics with accuracy and precision of better than 1 kcal/mol, and redesign of a complex protein-
RNA interface to accurately retarget silencing complexes in vivo. We propose herein to unify, rigorously test,
and disseminate our labs’ methods to tackle three separate but synergistic computational problems in protein-
RNA research: automated correction of errors that pervade experimental protein-RNA complex structures (Aim
1), our richest resources of protein-RNA information; prediction of impacts of mutation on RNA-protein
interaction energetics (Aim 2) that could highlight new regulatory links in disease-associated alleles; and
design of novel engineered RNA-protein interactions (Aim 3) to facilitate rational perturbation of genetic events
to aid biological inquiry and eventually to ameliorate disease. We will evaluate success within each of our Aims
through true blind predictions tested through rapidly emerging cryoelectron microscopy maps and repurposed
sequencers that can measure hundreds of thousands of RNA-protein affinities in single experiments and, more
broadly, by adoption of our Rosetta software and online tools by the general biomedical research community.
The proposed protein-RNA-focused research addresses an area of molecular modeling that has received
surprisingly little attention in the computational community but is unambiguously important for accelerating
biological understanding and molecular medicine.
总结
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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Philip Bradley其他文献
Philip Bradley的其他文献
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{{ truncateString('Philip Bradley', 18)}}的其他基金
Integrating T cell receptor features with gene expression profiles to define T cell specificity and differentiation
将 T 细胞受体特征与基因表达谱整合以定义 T 细胞特异性和分化
- 批准号:
10433774 - 财政年份:2022
- 资助金额:
$ 11.4万 - 项目类别:
Integrating T cell receptor features with gene expression profiles to define T cell specificity and differentiation
将 T 细胞受体特征与基因表达谱整合以定义 T 细胞特异性和分化
- 批准号:
10569090 - 财政年份:2022
- 资助金额:
$ 11.4万 - 项目类别:
Integrating T cell receptor features with gene expression profiles to define T cell specificity and differentiation
将 T 细胞受体特征与基因表达谱整合以定义 T 细胞特异性和分化
- 批准号:
10593429 - 财政年份:2022
- 资助金额:
$ 11.4万 - 项目类别:
Molecular modeling and machine learning for protein structures and interactions
蛋白质结构和相互作用的分子建模和机器学习
- 批准号:
10191763 - 财政年份:2021
- 资助金额:
$ 11.4万 - 项目类别:
Molecular modeling and machine learning for protein structures and interactions
蛋白质结构和相互作用的分子建模和机器学习
- 批准号:
10707065 - 财政年份:2021
- 资助金额:
$ 11.4万 - 项目类别:
Molecular modeling and machine learning for protein structures and interactions
蛋白质结构和相互作用的分子建模和机器学习
- 批准号:
10631595 - 财政年份:2021
- 资助金额:
$ 11.4万 - 项目类别:
Molecular modeling and machine learning for protein structures and interactions
蛋白质结构和相互作用的分子建模和机器学习
- 批准号:
10406274 - 财政年份:2021
- 资助金额:
$ 11.4万 - 项目类别:
Rational design and functionalization of circular tandem repeat proteins
环状串联重复蛋白的合理设计和功能化
- 批准号:
9301141 - 财政年份:2017
- 资助金额:
$ 11.4万 - 项目类别:
High-resolution modeling of protein-RNA interfaces
蛋白质-RNA 界面的高分辨率建模
- 批准号:
10013238 - 财政年份:2017
- 资助金额:
$ 11.4万 - 项目类别:
Rational design and functionalization of circular tandem repeat proteins
环状串联重复蛋白的合理设计和功能化
- 批准号:
9897572 - 财政年份:2017
- 资助金额:
$ 11.4万 - 项目类别:
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