Automated docking and modeling for electron microscopy

描述（由申请人提供）：活生物体在几乎每个生物过程中都依赖于对分子组的特异性识别。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。在这里，我们提出了一种新的方法，结合中间分辨率数据的配合物从电子显微镜与原子分辨率结构的复杂的组件，以获得可靠的原子模型的复杂的快速和自动的方式。所提出的方法相结合的相关统计为基础的对接和实空间细化的原子结构的密度来自电子显微镜与工具，从基于理论的蛋白质-蛋白质对接，灵活的结构对齐，和比较建模。我们将通过应用于肌动蛋白-talin复合物和细菌皮利来推动其发展。通过将新系统的开发与解决细胞生物学和生物医学中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表现的即时反馈，同时通过这些先进工具的应用提供有价值的见解。

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.