Accelerated Determination of 3D Structures of Proteins and Complexes
加速测定蛋白质和复合物的 3D 结构
基本信息
- 批准号:8840975
- 负责人:
- 金额:$ 44.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-05-03 至 2015-12-31
- 项目状态:已结题
- 来源:
- 关键词:AreaBacteriaBiologyCollaborationsComputational BiologyCrystallographyDNA SequenceData SetDevelopmentEntropyGenomic approachGenomicsHeadHealthHumanHybridsMapsMemorial Sloan-Kettering Cancer CenterMethodsMolecularMolecular ComputationsPharmaceutical PreparationsPhysicsPlanet MarsProtein FamilyProtein Structure InitiativeProteinsResearchRoentgen RaysSequence AlignmentSiteSolutionsStructureSystems BiologyTechnologyTertiary Protein StructureVertebral columnVirusWorkX-Ray Crystallographybasebiological researchexperiencefungusinternational centermedical schoolsmicroorganismnew technologyprogramsprotein complexprotein structurerapid growthstructural biologystructural genomicstargeted treatmenttherapeutic targetthree dimensional structure
项目摘要
DESCRIPTION (provided by applicant): The project will provide new technology to accelerate the discovery of protein structures and assemblies from humans and other species. Knowing the 3D structures of proteins has important biomedical implications for the development of protein-based therapies and targeted therapeutic drugs, but the 3D structures of proteins of thousands of important protein types remain unsolved. The project aims to close this gap, based on two recent advances: (1) the rapid development of new DNA sequencing technologies and (2) a recent breakthrough in protein 3D structure prediction using statistical physics and bio-molecular computation. The new structure prediction method, developed by the applicant team, extracts evolutionary residue-residue couplings from multiple sequence alignments, using a maximum entropy method. The team will use the evolutionary couplings as distance constraints to predict the structure of many single domains, of multidomain proteins and of protein complexes, and to map functional sites on known and predicted structures, with potentially broad impact on diverse biological research areas. The team will also aim to aid the development of hybrid computational- experimental technologies for structure determination. For X-ray crystallography, the aim is bridge the gap between the predicted 3D structures and the basin of convergence for molecular replacement, allowing structure determination from a single native data set without the need for anomalous or derivative diffraction datasets. For NMR, the aim is to add evolutionary couplings to NMR-derived backbone and residue-residue distance information and thus reduce experimental effort and/or permit the solution of larger structures. The project is a close collaboration between the Computational Biology Program at Memorial Sloan-Kettering Cancer Center and the Department of Systems Biology at Harvard Medical School. Experimental collaborations with PSI:Biology centers and the international structural genomics effort will aim to implement a more efficient technology for the determination of biomedically relevant protein structures.
描述(由申请人提供):该项目将提供新的技术,以加速从人类和其他物种中发现蛋白质结构和组装。了解蛋白质的3D结构对于基于蛋白质的疗法和靶向治疗药物的发展具有重要的生物医学意义,但数千种重要蛋白质类型的蛋白质的3D结构仍未解决。该项目旨在缩小这一差距,基于最近的两项进展:(1)新DNA测序技术的快速发展和(2)利用统计物理和生物分子计算在蛋白质三维结构预测方面的最新突破。由申请团队开发的新结构预测方法,使用最大熵方法从多个序列比对中提取进化残基-残基耦合。该团队将使用进化耦合作为距离约束来预测许多单一结构域、多结构域蛋白质和蛋白质复合体的结构,并绘制已知和预测结构上的功能位点图,这可能会对不同的生物学研究领域产生广泛影响。该团队还将致力于帮助开发用于结构确定的计算-实验混合技术。对于X射线结晶学,目的是弥合预测的3D结构和分子替换的收敛盆地之间的差距,允许从单个原始数据集确定结构,而不需要异常或派生的衍射数据集。对于核磁共振,其目标是将进化耦合添加到核磁共振衍生的骨架和残基-残基距离信息中,从而减少实验工作量和/或允许解决更大的结构。该项目是纪念斯隆-凯特琳癌症中心的计算生物学项目和哈佛医学院系统生物学系之间的密切合作。与PSI:生物中心和国际结构基因组学努力的实验合作将致力于实施一种更有效的技术来确定与生物医学相关的蛋白质结构。
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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CHRIS SANDER其他文献
CHRIS SANDER的其他文献
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{{ truncateString('CHRIS SANDER', 18)}}的其他基金
Accelerated Determination of 3D Structures of Proteins and Complexes
加速测定蛋白质和复合物的 3D 结构
- 批准号:
9059732 - 财政年份:2013
- 资助金额:
$ 44.2万 - 项目类别:
Accelerated Determination of 3D Structures of Proteins and Complexes
加速测定蛋白质和复合物的 3D 结构
- 批准号:
8483934 - 财政年份:2013
- 资助金额:
$ 44.2万 - 项目类别:
Pathway Commons: A Public Library of Biological Pathways
Pathway Commons:生物途径公共图书馆
- 批准号:
8549293 - 财政年份:2012
- 资助金额:
$ 44.2万 - 项目类别:
Pathway Commons: A Public Library of Biological Pathways
Pathway Commons:生物途径公共图书馆
- 批准号:
8243036 - 财政年份:2012
- 资助金额:
$ 44.2万 - 项目类别:
Pathway Commons: Research Resource for Biological Pathways
Pathway Commons:生物途径研究资源
- 批准号:
8935277 - 财政年份:2012
- 资助金额:
$ 44.2万 - 项目类别:
Pathway Commons: A Public Library of Biological Pathways
Pathway Commons:生物途径公共图书馆
- 批准号:
8698796 - 财政年份:2012
- 资助金额:
$ 44.2万 - 项目类别:
Pathway Commons: Research Resource for Biological Pathways
Pathway Commons:生物途径研究资源
- 批准号:
9357629 - 财政年份:2012
- 资助金额:
$ 44.2万 - 项目类别:
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