Integrated modeling of biological nanomachines

生物纳米机器的集成建模

• 批准号: 0705196
• 负责人: Andrej Sali
• 金额: --
• 依托单位: University of California-San Francisco
• 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=0705196&HistoricalAwards=false
• 关键词: Integrated; modeling; biological; nanomachines

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装。电子冷冻微观显微镜（冷冻）是确定生物纳米机器分子结构的最合适的结构工具，该工具通常由多个蛋白质亚基和/或核酸组成，总质量大于50万达尔顿。 目的是开发信息发现和集成方法，以推导纳米机器的原子模型。此类模型将与蛋白质折叠和信息学数据的物理学结合使用3维（3-D）冷冻质量密度函数（即体积密度图）。通过在计算机图形学，计算生物物理学，结构信息学和冷冻的五个研究者的专业知识的集成中，使该项目成为可能。这项研究的智力优点是通过从低分辨率，复杂的冷冻体积密度中提取结构信息的计算方法强调的，并将这些信息整合到经典蛋白质结构建模范式中，例如比较建模和从头开始建模，以了解生物学纳米机器。 这三个研究目标涉及拟议算法的信息发现，信息集成和验证。 拟议的研究将对三个不同学科产生重大影响：计算机科学，分子建模和冷冻。 此外，团队将自由地将其由此产生的工具传播到学术界，并将在项目结束时举办研讨会。为了增强其研究的影响，研究人员将与每个成员机构的教育相结合，以注重多样性。特别是，这些研究人员将在五个参与机构的研究生和高级本科生的生物纳米机器建模中开发虚拟教学课程。