UKRI/BBSRC - NSF/BIO: Modeling of protein interactions to predict phenotypic effects of genetic mutations
UKRI/BBSRC - NSF/BIO:蛋白质相互作用建模以预测基因突变的表型效应
基本信息
- 批准号:2224122
- 负责人:
- 金额:$ 93.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-12-15 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Structures of protein complexes are essential for interpretation of genetic mutations. Approaches to structural modeling of proteins and their interactions are rapidly developing, powered by advances in knowledge-based methods and better understanding of physical principles of protein structure and function. A vast amount of information on human genetic variation, including numerous single amino acid changes, is available from high-throughput sequencing. The project focuses on application of modeling techniques to the development of a public resource incorporating structural modeling with genetic amino acid variants and assessment of their functional impact. The long-term goals of this research are to gain insights into fundamental principles of molecular processes in living systems and the effect of genetic mutations on cellular mechanisms. This collaborative project combines highly complementary areas of expertise of the US team on modeling of protein interactions, and the UK team on protein structure prediction and missense variant effects. The teams will continue coordinating research and training activities, based on the project, with graduate and undergraduate programs locally, nationally and internationally. Minority students and women will be involved in different parts of the research. The project will enhance infrastructure for research and education. The US and UK teams have an extensive record of developing and disseminating public resources, used by many researchers worldwide. The project participants will be actively presenting their results at various multidisciplinary conferences and workshops.The approach incorporating predicted complexes in model organisms with genetic variants and their phenotypic effect assessment will be further developed. The objectives of the project are: (1) structural modeling of protein interactome; (2) assessment of phenotypic effects of genetic variation; and (3) public resource for structural characterization of protein interactome and phenotypic effects of genetic mutations. Computational approaches to structural characterization of protein complexes will incorporate recent advances in application of Deep Learning to prediction of protein structures and assemblies. The stereochemical approach to prediction of the mutation effect will involve modeling acceptable conformations for the variant side chains and evaluating the change in interactions. The GWYRE resource will incorporate protein complexes for model organisms, annotated by the phenotypic effects of missense variants. The project outcome will have a significant impact on the research field by development of the integrated public resource for structural characterization of protein interactomes and assessment of the phenotypic effects of genetic mutations. The results of the project will be available at http://www.gwyre.org and also at http://vakser.compbio.ku.edu and http://www.sbg.bio.ic.ac.uk.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
蛋白质复合物的结构对于解释基因突变至关重要。在基于知识的方法的进步以及对蛋白质结构和功能的物理原理的更好理解的推动下,蛋白质及其相互作用的结构建模方法正在迅速发展。通过高通量测序可以获得大量关于人类遗传变异的信息,包括大量的单一氨基酸变化。该项目的重点是应用建模技术来开发公共资源,将结构建模与遗传氨基酸变异相结合并评估其功能影响。这项研究的长期目标是深入了解生命系统中分子过程的基本原理以及基因突变对细胞机制的影响。该合作项目结合了美国团队在蛋白质相互作用建模方面和英国团队在蛋白质结构预测和错义变异效应方面的高度互补的专业知识领域。这些团队将根据该项目继续协调本地、国内和国际研究生和本科生项目的研究和培训活动。少数族裔学生和女性将参与研究的不同部分。该项目将加强研究和教育基础设施。美国和英国团队在开发和传播公共资源方面拥有丰富的记录,被世界各地的许多研究人员使用。项目参与者将在各种多学科会议和研讨会上积极展示他们的成果。将进一步开发将预测的复合物与遗传变异模型生物相结合及其表型效应评估的方法。该项目的目标是:(1)蛋白质相互作用组的结构建模; (2)遗传变异的表型效应评估; (3) 用于蛋白质相互作用组结构表征和基因突变表型效应的公共资源。蛋白质复合物结构表征的计算方法将结合深度学习在预测蛋白质结构和组装方面的应用的最新进展。预测突变效应的立体化学方法将涉及对变体侧链的可接受构象进行建模并评估相互作用的变化。 GWYRE 资源将整合模型生物的蛋白质复合物,并通过错义变体的表型效应进行注释。该项目的成果将通过开发用于蛋白质相互作用组结构表征和基因突变表型效应评估的综合公共资源,对研究领域产生重大影响。该项目的结果将在 http://www.gwyre.org、http://vakser.compbio.ku.edu 和 http://www.sbg.bio.ic.ac.uk 上提供。该奖项反映了 NSF 的法定使命,并通过使用基金会的智力价值和更广泛的影响审查标准进行评估,被认为值得支持。
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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Ilya Vakser其他文献
Ilya Vakser的其他文献
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{{ truncateString('Ilya Vakser', 18)}}的其他基金
Bilateral BBSRC-NSF/BIO: CIBR: Structural modeling of interactome to assess phenotypic effects of genetic variation.
双边 BBSRC-NSF/BIO:CIBR:相互作用组的结构模型,用于评估遗传变异的表型效应。
- 批准号:
1917263 - 财政年份:2019
- 资助金额:
$ 93.02万 - 项目类别:
Standard Grant
Bilateral BBSRC-NSF/BIO: ABI Innovation: Modeling protein interactions to interpret genetic variation
双边 BBSRC-NSF/BIO:ABI 创新:模拟蛋白质相互作用以解释遗传变异
- 批准号:
1565107 - 财政年份:2016
- 资助金额:
$ 93.02万 - 项目类别:
Standard Grant
ABI Innovation: Target - template structural and functional relationships in modeling of protein - protein interactions
ABI Innovation:蛋白质-蛋白质相互作用建模中的目标-模板结构和功能关系
- 批准号:
1262621 - 财政年份:2013
- 资助金额:
$ 93.02万 - 项目类别:
Continuing Grant
Conference: Modeling of Protein Interactions in Genomes to be held at the Lightsey Conference Center, in Charleston, SC on June 16-19, 2001
会议:基因组中蛋白质相互作用的建模将于 2001 年 6 月 16-19 日在南卡罗来纳州查尔斯顿的 Lightsey 会议中心举行
- 批准号:
0314290 - 财政年份:2003
- 资助金额:
$ 93.02万 - 项目类别:
Standard Grant
Development of GRAMM Method and Software for Protein-Protein Docking
蛋白质-蛋白质对接的 GRAMM 方法和软件的开发
- 批准号:
0296003 - 财政年份:2001
- 资助金额:
$ 93.02万 - 项目类别:
Continuing Grant
Conference: Modeling of Protein Interactions in Genomes to be held at the Lightsey Conference Center, in Charleston, SC on June 16-19, 2001
会议:基因组中蛋白质相互作用的建模将于 2001 年 6 月 16-19 日在南卡罗来纳州查尔斯顿的 Lightsey 会议中心举行
- 批准号:
0097883 - 财政年份:2001
- 资助金额:
$ 93.02万 - 项目类别:
Standard Grant
Development of GRAMM Method and Software for Protein-Protein Docking
蛋白质-蛋白质对接的 GRAMM 方法和软件的开发
- 批准号:
9808093 - 财政年份:1998
- 资助金额:
$ 93.02万 - 项目类别:
Continuing Grant
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