Informatics/modeling/extend/NMR structure determination

但前提是。 这项研究的长期目标是显著提高对蛋白质的理解速度。 信息学中基于物理的新模型的发展。蛋白质参与了大量的 生物功能及其与许多疾病和紊乱的关联使得 了解它们的结构是一个与人类健康密切相关的课题.作为迈向 了解蛋白质，开发广泛的蛋白质结构清单及其快速分析是 被指定为结构生物学的关键目标。实验方法将继续发挥关键作用， 由于大量新的蛋白质折叠仍未被探索。核磁共振波谱是一种关键的实验工具 分析蛋白质结构和精简和扩大其覆盖范围的强烈需求存在。初级阶段 这项工作的研究重点是调查和改进将导致显著速度的工具- UPS通过构建一个整合了信息学和 物理模型。策略是将信息学工具的使用与物理建模相结合，即 需要快速评估、合并多个数据源，并促进高效构建和分析 蛋白质库存。提议的方法已经导致了创新的工具，这些工具已经证明 核磁共振结构测定实践中的可量化进展。申请者有三项研究 此批款期间的目标：1)调查将PI开发的现有工具组合成 一个完整的范例，旨在解决中小型企业快速而稳健的结构确定问题 蛋白质大小，2)研究方法的蒸馏和扩展到一组核心工具中，这些工具可以形成 为快速确定蛋白质折叠和较大蛋白质结构的新工具奠定了基础，以及3)Take 了解以下问题的探索性步骤：“每个新工具对我们的 对蛋白质空间的理解。这些方法背后的基本思想是设计一系列物理 模型，并使用信息学工具来找到最“成功”的模型。这些工具将促进生产 通过加快和简化实验数据的使用，及时获得有关蛋白质功能的信息 结构确定中的数据。在理解蛋白质方面的加速进展将有一个直接的 并对推进人类健康保障产生重大影响。

PROVIDED. The long-term goal of this research is to provide significant speed-ups in understanding proteins through development of novel physics-based models in informatics. Proteins are involved in a large array of biological functions and their association with numerous diseases and disorders makes the timely understanding of their structure a subject with significant relevance to human health. As a step toward understanding proteins, the development of a broad inventory of protein structures and their rapid analysis is designated as a critical goal of structural biology. Experimental methods will continue to play a critical role, as a large number of novel protein folds remain unexplored. NMR spectroscopy is a key experimental tool in analyzing protein structures and a strong need for streamlining and extending its reach exists. The primary research focus of this work is the investigation and advancement of tools that will lead to significant speed- ups in understanding protein structures by building a probabilistic framework that integrates informatics and physical models. The strategy is to combine the use of informatics tools and physical modeling that is needed in order to rapidly evaluate, merge multiple data sources, and facilitate efficient building and analysis of protein inventories. The proposed approach, has already lead to innovative tools that have demonstrated quantifiable advances in the practice of NMR structure determination. The applicant has three research goals during this grant period: 1) investigate approaches to combining present tools developed by the PI into a complete paradigm with the aim of addressing fast and robust structure determination of small to moderate size proteins, 2) investigate distillation and extension of methods into a set of core tools that could form the basis for novel tools for rapid determination of protein folds and structure of larger proteins, and 3) take exploratory steps toward understanding the question of "how much each new tool contributes to our understanding of protein space." The basic idea behind these methods is to devise a family of physical models and use informatics tools to find the most 'successful' model. These tools will facilitate production of timely information regarding proteins' functions by speeding up and streamlining the use of experimental data in structure determination. The accelerated progress toward understanding proteins will have a direct and significant impact on advancing the safeguards of human health.