III-CXT: Collaborative Research: Integrated Modeling of Biological Nanomachines

III-CXT：协作研究：生物纳米机器的集成建模

• 批准号: 0705474
• 负责人: Matthew Baker
• 金额: $ 16.5万
• 依托单位: Baylor College of Medicine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0705474&HistoricalAwards=false
• 关键词: III; CXT; Collaborative; Research; Integrated

Biological nanomachines are the assemblies that carry out all the basic biological processes in a living organism. Electron cryo-microscopy (cryoEM) is the most appropriate structural tool to determine molecular structures of biological nanomachines that generally consist of multiple protein subunits and/or nucleic acids with a total mass greater than 0.5 million Daltons. The goal is to develop information discovery and integration methodologies for deriving atomic models of nanomachines. Such models will be derived from 3-dimensional (3-D) cryoEM mass density function (i.e. a volumetric density map) in conjunction with physics of protein folding and informatics data. This project is made possible by an integration of the expertise of five investigators in computer graphics, computational biophysics, structural informatics and cryoEM. The intellectual merit of this research is highlighted by the computational approaches of extracting structural information from low-resolution, complex cryoEM volume densities and integrating this information into classical protein structure modeling paradigms, such as comparative modeling and ab initio modeling, for understanding biological nanomachines. The three research goals involve information discovery, information integration and validation of the proposed algorithms. The proposed research will have significant impacts in three disparate disciplines: computer science, molecular modeling, and cryoEM. Furthermore, the team will disseminate their resulting tools freely to the academic community and will host a workshop towards the end of the project. To enhance the impact of their research, the investigators will integrate research with education at each member institution with an eye towards diversity. In particular, these investigators will develop a virtual didactic course in modeling of biological nanomachines for graduate and senior undergraduate students at the five participating institutions.

生物纳米机器是在生物体中执行所有基本生物过程的组件。冷冻电子显微镜 (cryoEM) 是确定生物纳米机器分子结构的最合适的结构工具，生物纳米机器通常由多个蛋白质亚基和/或总质量大于 50 万道尔顿的核酸组成。 目标是开发信息发现和集成方法来推导纳米机器的原子模型。此类模型将源自 3 维 (3-D) 冷冻电镜质量密度函数（即体积密度图），并结合蛋白质折叠物理学和信息学数据。该项目是通过整合计算机图形学、计算生物物理学、结构信息学和冷冻电镜领域五名研究人员的专业知识而得以实现的。这项研究的智力价值体现在从低分辨率、复杂的冷冻电镜体积密度中提取结构信息并将这些信息集成到经典蛋白质结构建模范式（例如比较建模和从头建模）中的计算方法中，以了解生物纳米机器。 这三个研究目标涉及信息发现、信息集成和所提出算法的验证。 拟议的研究将对三个不同的学科产生重大影响：计算机科学、分子建模和冷冻电镜。 此外，该团队将向学术界免费传播他们的工具，并将在项目结束时举办研讨会。为了增强研究的影响力，研究人员将把每个成员机构的研究与教育结合起来，着眼于多样性。特别是，这些研究人员将为五个参与机构的研究生和高年级本科生开发生物纳米机器建模的虚拟教学课程。