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
• 负责人: Ilya Vakser
• 金额: $ 95.7万
• 依托单位: University of Kansas Center for Research Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1917263&HistoricalAwards=false
• 关键词: Bilateral; BBSRC; NSF; BIO; CIBR

Structural characterization of protein interactions is essential for interpretation of genetic variation. A vast amount of information on single amino acid variants will be available from sequencing. The project focuses on application of computational approaches to the development of a public resource incorporating structural modeling with genetic amino acid variants and assessment of their functional impact. The resource will facilitate better understanding of principles of protein interaction and structure/function relationships. The long-term goal of this research is to gain insights into fundamental principles of molecular processes in living systems, leading to structure-based description of the cell. The collaborative project combines highly complementary areas of expertise of the US team, on high-throughput modeling of protein-protein interactions, and the UK team, on protein structure prediction and effects of genetic variation. The teams will coordinate 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, including those within established minority-oriented programs. The project will enhance infrastructure for research and education. The US and UK teams have an extensive and well proven 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 project will continue development of an integrated approach to high-throughput modeling of proteins and their complexes. The objectives of the project are: (1) to develop advanced high-throughput approaches to modeling of protein interactome; (2) to provide assessment of phenotypic effects of genetic variation; and (3) to develop and implement genome-wide resource for structural characterization of interactome and phenotypic effects of genetic variation. The structure modeling approaches will be based on new search, scoring and refinement strategies, and will integrate the tertiary and quaternary structure prediction. The prediction of the mutation effect will evaluate the change in protein interactions. The genome-wide GWYRE resource will incorporate structurally refined protein complexes for model organisms annotated by the phenotypic effects of the single amino acid variants. The project outcome will have a significant impact on the research field by integrating template-based tertiary and quaternary structure prediction, and development of a comprehensive public resource for structural characterization of interactomes and assessment of phenotypic effects of genetic variation. 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.

蛋白质相互作用的结构特征对于解释遗传变异是必不可少的。测序将提供大量关于单一氨基酸变体的信息。该项目的重点是将计算方法应用于公共资源的开发，将结构建模与遗传氨基酸变种结合起来，并评估其功能影响。该资源将有助于更好地理解蛋白质相互作用和结构/功能关系的原理。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，导致对细胞的基于结构的描述。该合作项目结合了美国团队和英国团队在高通量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遗传变异影响方面的高度互补的专业知识领域。这些团队将根据该项目，与当地、国内和国际的研究生和本科生项目协调研究和培训活动。少数族裔学生和女性将参与这项研究的不同部分，包括那些已建立的面向少数族裔的项目。该项目将加强研究和教育的基础设施。美国和英国的团队在开发和传播公共资源方面拥有广泛且得到证实的记录，世界各地的许多研究人员都在使用这些资源。项目参与者将在各种多学科会议和讲习班上积极介绍他们的成果。该项目将继续开发一种对蛋白质及其复合体进行高通量建模的综合方法。该项目的目标是：(1)开发先进的高通量方法来模拟蛋白质相互作用组；(2)提供遗传变异的表型效应的评估；以及(3)开发和实施全基因组资源，用于相互作用组的结构表征和遗传变异的表型效应。结构建模方法将基于新的搜索、评分和精化策略，并将整合三级和四级结构预测。突变效应的预测将评估蛋白质相互作用的变化。全基因组的GWYRE资源将包括模式生物的结构精炼的蛋白质复合体，通过单一氨基酸变体的表型效应进行注释。项目成果将对研究领域产生重大影响，因为它整合了基于模板的三级和四级结构预测，并开发了一个全面的公共资源，用于确定相互作用的结构特征和评估遗传变异的表型效应。该项目的结果将在http://www.gwyre.org和http://vakser.compbio.ku.edu上公布，http://www.sbg.bio.ic.ac.uk.This奖反映了国家科学基金会的法定使命，并通过使用基金会的智力优势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

Dockground resource for protein recognition studies

• DOI: 10.1002/pro.4481
• 发表时间: 2022-12-01
• 期刊: PROTEIN SCIENCE
• 影响因子: 8
• 作者: Collins，Keeley W.;Copeland，Matthew M.;Vakser，Ilya A.
• 通讯作者: Vakser，Ilya A.

Text mining for modeling of protein complexes enhanced by machine learning

• DOI: 10.1093/bioinformatics/btaa823
• 发表时间: 2021-02-15
• 期刊: BIOINFORMATICS
• 影响因子: 5.8
• 作者: Badal，Varsha D.;Kundrotas，Petras J.;Vakser，Ilya A.
• 通讯作者: Vakser，Ilya A.

Application of docking methodologies to modeled proteins

• DOI: 10.1002/prot.25889
• 发表时间: 2020-03-20
• 期刊: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
• 影响因子: 2.9
• 作者: Singh, Amar;Dauzhenka, Taras;Vakser, Ilya A.
• 通讯作者: Vakser, Ilya A.