Automated docking and modeling for electron microscopy

电子显微镜自动对接和建模

基本信息

批准号：
8018308
负责人：
NIELS VOLKMANN
金额：
$ 13.74万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-24 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8018308
关键词：
Accounting Actin-Binding Protein Actins Actomyosin Address Affinity Algorithms Atomic Resolution X-Ray Crystallography Bacterial Pili Bacterial Typing Binding Bioinformatics Biological Biological Models Biological Process Biology Boston Cells Cellular biology Chemistry Cholera Collaborations Collection Communities Complex Computational Technique Computers Couples Coupling Crystallography Cytoskeletal Proteins Data Decision Making Development Docking Electron Microscopy Electrons Environment Escherichia coli Exhibits Feedback Fiber Florida Gold Head Homology Modeling Imagery Individual Institutes Integrins Life Ligands Manuals Medical Menin Methodology Methods Microfilaments Modeling Mole the mammal Molecular Biology Molecular Structure Moraxella (Moraxella) bovis Myosin ATPase NMR Spectroscopy Neisseria Neisseria gonorrhoeae Nuclear Magnetic Resonance Nucleotides Organism Performance Pilum Process Proteins Pseudomonas Pythons Research Personnel Resolution Roentgen Rays Specimen Staging Structure System Talin Techniques Tertiary Protein Structure Testing Tin United States National Institutes of Health Universities Validation Virulence Virus Work X-Ray Crystallography adhesion receptor aqueous base comparative density flexibility improved insight macromolecular assembly molecular assembly/self assembly molecular recognition novel strategies pathogen programs protein protein interaction reconstruction single molecule statistics structural genomics tegrin theories tool user-friendly

项目摘要

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）：生物体几乎在每个生物过程中都依赖于分子组的特定识别。因此，理解分子识别和确定分子复合物结构的重要性怎么估计都不为过。在这里，我们建议开发一种新方法，将电子显微镜中复合物的中间分辨率数据与复合物成分的原子分辨率结构相结合，以便以快速、自动的方式获得复合物的可靠原子模型。所提出的方法将基于相关统计的对接和原子结构的真实空间细化结合到电子显微镜得出的密度中，以及基于理论的蛋白质-蛋白质对接、灵活的结构对齐和比较建模的工具。我们将通过肌动蛋白-肌蛋白复合物和细菌菌毛的应用来推动开发。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，我们将获得有关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。