MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)
MINOS(通过散射优化核酸的大分子见解)
基本信息
- 批准号:8656719
- 负责人:
- 金额:$ 53.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-06-01 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:Active SitesAreaBindingBiologicalBiologyCell physiologyChemistryCollaborationsCommunitiesComplementComplexComputing MethodologiesCrystallizationCrystallographyDNADNA RepairDNA biosynthesisData CollectionDatabasesDefectDevelopmentDiseaseEukaryotaFosteringFunctional RNAGenetic TranscriptionGoalsHomology ModelingHumanHybridsImaging technologyIndividualInstructionKnowledgeLearningLigandsLinkMedicineMethodsMetricModificationMolecular BiologyMolecular ConformationMutationNatureNucleic AcidsOutcomeOutputPrincipal InvestigatorProductivityProtein Structure InitiativeProteinsProteomeRNARNA IRNA SplicingResearchResearch PersonnelResolutionRoentgen RaysRunningSamplingScientistShapesSolutionsStructural ChemistryStructureTechniquesTechnologyTestingTranscriptional RegulationWorkX-Ray CrystallographyXeroderma Pigmentosum Complementation Group BXeroderma Pigmentosum Complementation Group Dbasebeamlinedensityflexibilityhuman diseaseinnovationinsightmacromoleculenew technologynucleic acid binding proteinparticlepleiotropismpreventprotein complexresearch studyscreeningstructural biologysuccesstooltranscription factortranscription factor TFIIHtumor
项目摘要
MINOS will develop new methods and techniques to test the hypothesis that changes in conformation
and/or assembly determine biological outcomes. The staff and scientists of the SIBYLS beamline provide
comprehensive expertise in the targeted areas of nucleic acid binding proteins. High Throughput (HT) Small
Angle X-ray Scattering (SAXS), Macromolecular Crystallography (MX), and hybrid computational methods.
MINOS builds upon our results developing and employing SAXS to define accurate conformations and
assemblies in solution in combination with PSI high-resolution crystal structures for detail. Biological
information involves changes in shape as well as active site chemistry. SAXS provides robust analyses of
shape and conformational change in solution whereas crystallography provides precise information on
structural chemistry. Leveraging our existing SAXS and molecular biology expertise, we will innovate new
methods and technologies to integrate and advance PSI and community characterizations of key human
proteins and their complexes (with partner proteins, DNA, and RNA). MINOS will work closely with PSI
centers and individual researchers to identify promising targets and constructs, optimize solution conditions,
and provide solution conformation and assembly results that complement PSI high resolution crystal
structures. MINOS will provide new methods, tools, and strategies to characterize key human and higher
eukaryotes proteins and their complexes for structural biology and medicine, which have been challenging
for current PSI and community efforts. Technical goals include identifying and optimizing SAXS data
collection strategies for human proteins and their complexes in concert with high resolution structural
studies within the PSI centers, rescuing stalled protein targets, and developing hybrid methods and
techniques for easing the bottlenecks that currently place real limits on overall PSI productivity. The
Specific Aims will endeavor to 1) develop and apply innovative HT SAXS methods to solve solution
structures of PSLBiology defined targets, and 2) use solution scattering technologies to link PSI and
community structures to biology. Structures determined by PSI and community collaborations will direct
SAXS experiments, test functional implications from SAXS structures,, and provide critical details for
defining conformational trajectories in solution. Collectively the proposesd Aims provide a clear path to
leverage PSI 'and research community strengths and technologies for imaging human and higher eukaryote
proteins and their complexes with major impacts on biological understanding.
RELEVANCE (See instructions):
Preventing and treating human disease ultimately relies on an understanding of how proteins, DNA, and
RNA control key cellular functions. A major aspect of understanding these key macromolecules is a detailed
picture of their shape, flexibility, and dynamic nature. MINOS aims to provide new technologies and
methods to study dynamic human macromolecules for structural biology and medicine, and will test the
hypothesis that changes in the shape and assembly of dynamic macromolecules control biological
outcomes in predictable ways, thereby aiding our ability to predict and treat human disease.
MINOS将开发新的方法和技术来测试构象变化的假设,
和/或组装决定生物学结果。SIBYLS光束线的工作人员和科学家提供了
在核酸结合蛋白的目标领域的全面专业知识。高吞吐量(HT)小
角X射线散射(SAXS)、大分子晶体学(MX)和混合计算方法。
MINOS基于我们的研究结果,开发和使用SAXS来定义准确的构象,
在溶液中的组装结合PSI高分辨率晶体结构的细节。生物
信息涉及形状的变化以及活性部位化学。SAXS提供了强大的分析,
而晶体学提供了关于溶液中的形状和构象变化的精确信息,
结构化学利用我们现有的SAXS和分子生物学专业知识,我们将创新
方法和技术,以整合和推进PSI和社区表征的关键人
蛋白质及其复合物(与伴侣蛋白、DNA和RNA)。MINOS将与PSI密切合作
中心和个人研究人员,以确定有前途的目标和建设,优化解决方案的条件,
并提供补充PSI高分辨率晶体的溶液构象和组装结果
结构. MINOS将提供新的方法、工具和战略,
真核生物蛋白质及其复合物的结构生物学和医学,这一直是具有挑战性的
目前的PSI和社区的努力。技术目标包括识别和优化SAXS数据
人类蛋白质及其复合物的收集策略与高分辨率结构
PSI中心内的研究,拯救停滞的蛋白质目标,并开发混合方法,
缓解目前对PSI整体生产力造成真实的限制的瓶颈的技术。的
Specific Aims将奋进1)开发和应用创新的HT SAXS方法来解决问题
结构的PSLBiology定义的目标,和2)使用解决方案散射技术,以链接PSI和
社区结构到生物学。由PSI和社区合作确定的结构将指导
SAXS实验,测试SAXS结构的功能含义,并为
定义溶液中的构象轨迹。总的来说,拟议的目标提供了一条明确的道路,
利用PSI和研究团体的优势和技术对人类和高等真核生物进行成像
蛋白质及其复合物对生物学的理解有重大影响。
相关性(参见说明):
预防和治疗人类疾病最终依赖于对蛋白质、DNA和
RNA控制关键的细胞功能。了解这些关键大分子的一个主要方面是详细的
它们的形状、灵活性和动态特性的图片。MINOS旨在提供新技术,
方法研究动态人体大分子结构生物学和医学,并将测试
动态大分子的形状和组装的变化控制生物学的假说
以可预测的方式,从而帮助我们预测和治疗人类疾病的能力。
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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John A. Tainer其他文献
Molecular model of TFIIH recruitment to the transcription-coupled repair machinery
TFIIH 招募到转录偶联修复机制的分子模型
- DOI:
10.1038/s41467-025-57593-0 - 发表时间:
2025-03-08 - 期刊:
- 影响因子:15.700
- 作者:
Tanmoy Paul;Chunli Yan;Jina Yu;Susan E. Tsutakawa;John A. Tainer;Dong Wang;Ivaylo Ivanov - 通讯作者:
Ivaylo Ivanov
DNA repair without flipping out
DNA 修复而不抓狂
- DOI:
10.1038/nature15646 - 发表时间:
2015-10-28 - 期刊:
- 影响因子:48.500
- 作者:
David S. Shin;John A. Tainer - 通讯作者:
John A. Tainer
A prismatic view of the epigenetic-metabolic regulatory axis in breast cancer therapy resistance
乳腺癌治疗耐药中表观遗传-代谢调节轴的棱柱形视图
- DOI:
10.1038/s41388-024-03054-9 - 发表时间:
2024-05-08 - 期刊:
- 影响因子:7.300
- 作者:
Chandrima Das;Apoorva Bhattacharya;Swagata Adhikari;Atanu Mondal;Payel Mondal;Santanu Adhikary;Siddhartha Roy;Kenneth Ramos;Kamlesh K. Yadav;John A. Tainer;Tej K. Pandita - 通讯作者:
Tej K. Pandita
Multiscale Modeling of PCNA - Ubiquitin Interactions
- DOI:
10.1016/j.bpj.2009.12.2087 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Ivaylo Ivanov;Adam Van Wynsberghe;John A. Tainer;J. Andrew McCammon - 通讯作者:
J. Andrew McCammon
Proteines de fusion ciblees par clycosaminoglycane, leurs conception, construction et compositions
糖胺聚糖融合蛋白、概念、结构和成分
- DOI:
- 发表时间:
1991 - 期刊:
- 影响因子:0
- 作者:
John A. Tainer;Leslie A. Kuhn;Maurice Boissinot;Cindy L. Fisher;Hans E. Parge;J. H. Griffin;Guy Mullenbach;Robert A. Hallewell - 通讯作者:
Robert A. Hallewell
John A. Tainer的其他文献
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{{ truncateString('John A. Tainer', 18)}}的其他基金
Mesocale And Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)
DNA 修复复合物结构集成的介观和纳米技术 (MANTIS-DRC)
- 批准号:
10687040 - 财政年份:2018
- 资助金额:
$ 53.43万 - 项目类别:
Mesocale And Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)
DNA 修复复合物结构集成的介观和纳米技术 (MANTIS-DRC)
- 批准号:
10251045 - 财政年份:2018
- 资助金额:
$ 53.43万 - 项目类别:
MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)
MINOS(通过散射优化核酸的大分子见解)
- 批准号:
8840824 - 财政年份:2012
- 资助金额:
$ 53.43万 - 项目类别:
MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)
MINOS(通过散射优化核酸的大分子见解)
- 批准号:
8469234 - 财政年份:2012
- 资助金额:
$ 53.43万 - 项目类别:
MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)
MINOS(通过散射优化核酸的大分子见解)
- 批准号:
8475491 - 财政年份:2012
- 资助金额:
$ 53.43万 - 项目类别:
Structural Biology of XPB and XPD Helicases
XPB 和 XPD 解旋酶的结构生物学
- 批准号:
8212285 - 财政年份:2006
- 资助金额:
$ 53.43万 - 项目类别:
Structural Biology of XPB and XPD Helicases
XPB 和 XPD 解旋酶的结构生物学
- 批准号:
7767763 - 财政年份:2006
- 资助金额:
$ 53.43万 - 项目类别:
Structural Biology of XPB and XPD Helicases
XPB 和 XPD 解旋酶的结构生物学
- 批准号:
7096103 - 财政年份:2006
- 资助金额:
$ 53.43万 - 项目类别:
Structural Biology of XPB and XPD Helicases
XPB 和 XPD 解旋酶的结构生物学
- 批准号:
7563283 - 财政年份:2006
- 资助金额:
$ 53.43万 - 项目类别:
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