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
• 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/8840824
• 关键词: Active Sites; Area; Binding; Binding Proteins; 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; Goals; Homology Modeling; Human; Hybrids; Imaging technology; Individual; Instruction; Knowledge; Learning; Ligands; Link; Medicine; Methods; Modification; Molecular Biology; Molecular Conformation; Mutation; Nature; Nucleic Acids; Outcome; Productivity; Protein Structure Initiative; Protein p53; Proteins; Proteome; RNA; RNA Splicing; Research; Research Personnel; Resolution; Roentgen Rays; Scientist; Shapes; Solutions; Structural Chemistry; Structure; Techniques; Technology; Testing; Transcriptional Regulation; Tumor Suppressor Proteins; 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; screening; structural biology; success; tool; transcription factor; transcription factor TFIIH

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 PSI:Biology 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 proposed 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.

MINOS将开发新的方法和技术来测试构象变化的假设