Automated docking and modeling for electron microscopy

电子显微镜自动对接和建模

• 批准号: 7144822
• 负责人: NIELS VOLKMANN
• 金额: $ 31.52万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7144822
• 关键词: Internet; actin binding protein; automated data processing; bioimaging /biomedical imaging; computer graphics /printing; computer human interaction; computer simulation; computer system design /evaluation; conformation; electron microscopy; image processing; macromolecule; mathematical model; pilin; protein protein interaction; protein structure function; structural biology

DESCRIPTION (provided by applicant): Living organisms rely on the specific recognition of groups of molecules in practically every biological process. Hence, the importance of understanding molecular recognition and determining the structures of molecular complexes cannot be overestimated. Here we propose the development of a new approach that combines intermediate resolution data of complexes from electron microscopy with atomic-resolution structures of the complex components in order to obtain reliable atomic models of the complex in a fast and automatic fashion. The proposed approach combines correlation-statistics based docking and real-space refinement of the atomic structures into the density derived by electron microscopy with tools from theory based protein-protein docking, flexible structure alignment, and comparative modeling. We will drive the development through applications to actin-talin complexes and bacterial pili. By coupling the development of the new system with applications that address fundamental question in cell biology and biomedicine, we will obtain immediate feedback as to how our approach performs in practice while providing valuable insights through the application of these advanced tools.

描述（由申请人提供）：活生物体在几乎每一个生物过程中都依赖于对分子群的特定识别。因此，理解分子识别和确定分子复合物结构的重要性不能被高估。在此，我们提出了一种新的方法，将电子显微镜的中间分辨率数据与复杂组分的原子分辨率结构相结合，以便快速、自动地获得可靠的配合物的原子模型。该方法结合了基于相关统计的对接和原子结构的实空间细化，利用基于理论的蛋白质-蛋白质对接、柔性结构对齐和比较建模等工具，通过电子显微镜导出密度。我们将通过应用于肌动蛋白-talin复合物和细菌菌毛来推动发展。通过将新系统的开发与解决细胞生物学和生物医学基本问题的应用相结合，我们将获得关于我们的方法在实践中如何执行的即时反馈，同时通过这些先进工具的应用提供有价值的见解。