Informatics/modeling/extend/NMR structure determination

信息学/建模/扩展/NMR结构测定

• 批准号: 7021075
• 负责人: HAMID R EGHBALNIA
• 金额: $ 13.32万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2009-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7021075
• 关键词: informatics; model; protein structure; proteins

DESCRIPTION: 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 speedups 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.

说明： 这项研究的长期目标是通过信息学中新的基于物理的模型的开发，显著加快理解蛋白质的速度。蛋白质参与了大量的生物学功能，它们与许多疾病和障碍的联系使得及时了解它们的结构成为与人类健康密切相关的课题。作为了解蛋白质的一个步骤，发展广泛的蛋白质结构清单及其快速分析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，因为大量新的蛋白质折叠仍未被探索。核磁共振波谱是分析蛋白质结构的关键实验工具，存在着简化和扩展其覆盖范围的强烈需求。这项工作的主要研究重点是调查和改进工具，这些工具将通过建立一个整合信息学和物理模型的概率框架来显著加速理解蛋白质结构。该战略是将信息学工具的使用与所需的物理建模结合起来，以便快速评估、合并多个数据源，并促进蛋白质库存的有效建立和分析。建议的方法已经导致了创新的工具，在核磁共振结构确定的实践中展示了可量化的进展。申请者在这一资助期间有三个研究目标：1)研究将PI开发的现有工具组合成一个完整的范例的方法，目的是解决中小尺寸蛋白质的快速和稳健的结构确定问题；2)研究方法的蒸馏和扩展，使其成为一套核心工具，可以形成快速确定蛋白质折叠和较大蛋白质结构的新工具的基础；以及3)采取探索性步骤，以了解“每个新工具对我们对蛋白质空间的理解有多大贡献”的问题。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。这些工具将通过加快和简化结构确定中实验数据的使用，促进有关蛋白质功能的及时信息的产生。在理解蛋白质方面的加速进展将对推进人类健康保障产生直接和重大的影响。