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/或组装确定生物学结果。 Sibyls束线的工作人员和科学家提供 核酸结合蛋白的靶向区域的全面专业知识。高通量（HT）小 角度X射线散射（SAXS），大分子晶体学（MX）和混合计算方法。 MINOS建立在我们开发和采用SAX的结果基础上，以定义准确的构象和 溶液中的组件与PSI高分辨率晶体结构结合使用。生物 信息涉及形状变化以及主动部位化学。 SAXS提供了强大的分析 溶液的形状和构象变化，而晶体学则提供了有关的精确信息 结构化学。利用我们现有的SAXS和分子生物学专业知识，我们将创新新的 整合和推进PSI以及关键人类的社区特征的方法和技术 蛋白质及其复合物（带有伴侣蛋白，DNA和RNA）。 MINOS将与PSI紧密合作 中心和个人研究人员确定有希望的目标和构造，优化解决方案条件， 并提供溶液构象和组装结果，以补充PSI高分辨率晶体 结构。 MINOS将提供新的方法，工具和策略来表征关键人物和更高的人 真核生物蛋白及其结构生物学和医学的复合物，这些蛋白质一直具有挑战性 用于当前的PSI和社区努力。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，营救停滞的蛋白质靶标，并开发混合方法和 放松目前对PSI总体生产率施加真正限制的瓶颈的技术。这 具体目标将努力1）开发和应用创新的HT SAXS方法来解决解决方案 PSLBIology定义目标的结构，以及2）使用溶液散射技术将PSI和 生物学的社区结构。由PSI和社区合作确定的结构将指导 SAXS实验，SAXS结构的测试功能含义，并为 定义溶液中的构象轨迹。总共提出的目标为 利用PSI和研究社区的优势和技术来成像人类和更高的真核生物 蛋白质及其复合物对生物学理解产生重大影响。 相关性（请参阅说明）： 防止和治疗人类疾病最终依赖于了解蛋白质，DNA和 RNA控制钥匙细胞功能。理解这些关键大分子的主要方面是详细的 图片的形状，灵活性和动态性质。 MINOS旨在提供新技术和 研究动态人类大分子的结构生物学和医学的方法，并将测试 假设动态大分子的形状和组装控制生物学 以可预测的方式结局，从而有助于我们预测和治疗人类疾病的能力。