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
• 负责人: John A. Tainer
• 金额: $ 53.43万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/8469234
• 关键词: Active Sites; Area; Binding; Biological; Biology; Cell physiology; Chemistry; Collaborations; Communities; Complement; Complex; Computing Methodologies; Crystallization; Crystallography; DNA; DNA Repair; DNA biosynthesis; Data Collection; Databases; Defect; Development; Disease; Eukaryota; Fostering; Functional RNA; Genetic Transcription; Goals; Homology Modeling; Human; Hybrids; Imaging technology; Individual; Instruction; Knowledge; Learning; Ligands; Link; Medicine; Methods; Metric; Modification; Molecular Biology; Molecular Conformation; Mutation; Nature; Nucleic Acids; Outcome; Output; Principal Investigator; Productivity; Protein Structure Initiative; Proteins; Proteome; RNA; RNA I; RNA Splicing; Research; Research Personnel; Resolution; Roentgen Rays; Running; Sampling; Scientist; Screening procedure; Shapes; Solutions; Structural Chemistry; Structure; Techniques; Technology; Testing; Transcriptional Regulation; Work; X-Ray Crystallography; Xeroderma Pigmentosum Complementation Group B; Xeroderma Pigmentosum Complementation Group D; base; beamline; density; flexibility; human disease; innovation; insight; macromolecule; new technology; nucleic acid binding protein; particle; pleiotropism; prevent; protein complex; research study; structural biology; success; tool; transcription factor; transcription factor TFIIH; tumor

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检验构象变化的假设 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 核酸结合蛋白目标领域的全面专业知识。高吞吐量 (HT) 小 角 X 射线散射 (SAXS)、高分子晶体学 (MX) 和混合计算方法。 MINOS 基于我们开发和使用 SAXS 的结果来定义准确的构象和 解决方案中的组件与 PSI 高分辨率晶体结构相结合以获得详细信息。生物 信息涉及形状以及活性位点化学的变化。 SAXS 提供稳健的分析 溶液中的形状和构象变化，而晶体学提供了精确的信息 结构化学。利用我们现有的 SAXS 和分子生物学专业知识，我们将创新新的 整合和推进 PSI 和关键人类社区特征的方法和技术 蛋白质及其复合物（与伙伴蛋白质、DNA 和 RNA）。 MINOS将与PSI密切合作 中心和个人研究人员确定有前途的目标和结构，优化解决方案条件， 并提供解决方案构象和组装结果，以补充 PSI 高分辨率晶体 结构。 MINOS 将提供新的方法、工具和策略来描述关键人类和更高层次的特征 真核生物蛋白质及其复合物在结构生物学和医学中的应用一直具有挑战性 用于当前 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相结合 PSI 中心内的研究，拯救停滞的蛋白质目标，并开发混合方法和 缓解目前对整体 PSI 生产力造成真正限制的瓶颈的技术。这 具体目标将致力于 1) 开发并应用创新的 HT SAXS 方法来解决解决方案 PSLBiology 定义目标的结构，2) 使用溶液散射技术将 PSI 和 生物学的群落结构。 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，并提供关键细节 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 和研究界的优势和技术对人类和高等真核生物进行成像 对生物学理解有重大影响的蛋白质及其复合物。 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了解 它们的形状、灵活性和动态性质的图片。 MINOS 旨在提供新技术和 研究结构生物学和医学动态人类大分子的方法，并将测试 动态大分子的形状和组装的变化控制生物的假设 以可预测的方式产生结果，从而帮助我们预测和治疗人类疾病的能力。