MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)

Minos将开发新的方法和技术来测试构象变化的假设 和/或组装决定生物结果。SIBYLS光束线的工作人员和科学家提供 在核酸结合蛋白的目标领域拥有全面的专业知识。高吞吐量(HT)小型 角X射线散射(SAXS)、大分子结晶学(MX)和混合计算方法。 Minos在我们结果的基础上开发和使用SAXS来定义准确的构象和 溶液中的组件与PSI高分辨率晶体结构相结合，以获得详细信息。生物学 信息涉及形状的变化以及活性中心化学。SAXS提供了可靠的分析 溶液中的形状和构象变化，而结晶学提供了关于 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 集成和改进关键人员的PSI和社区特征的方法和技术 蛋白质及其复合体(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以确定有希望的目标和结构，优化溶液条件， 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、工具和策略来表征关键的人类和更高 真核生物蛋白质及其复合体在结构生物学和医学中的应用一直是具有挑战性的 为当前的PSI和社区努力。技术目标包括识别和优化SAXS数据 结合高分辨结构的人类蛋白质及其复合体的收集策略 在PSI中心内进行研究，拯救停滞不前的蛋白质靶点，并开发杂交方法和 缓解目前对整体PSI生产率造成实际限制的瓶颈的技术。这个 具体目标将致力于1)开发和应用创新的HT SAXS方法来解决问题 PSL生物学定义的靶点的结构，以及2)使用溶液散射技术将PSI和 从群落结构到生物学。由PSI和社区协作确定的结构将指导 SAXS实验，测试SAXS结构的功能含义，并提供以下关键细节 定义溶液中的构象轨迹。总体而言，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 蛋白质及其复合体对生物学理解有重大影响。 相关性(请参阅说明)： 预防和治疗人类疾病最终取决于对蛋白质、DNA和 RNA控制着关键的细胞功能。理解这些关键大分子的一个主要方面是详细的 它们的形状、灵活性和动态性质的图片。Minos旨在提供新技术和 方法研究用于结构生物学和医学的动态人类大分子，并将测试 动态大分子形状和组装的变化控制生物的假说 结果以可预测的方式，从而有助于我们预测和治疗人类疾病的能力。

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.