Comprehensive Local Resolution Analysis for Cryo-EM

冷冻电镜的综合局部分辨率分析

基本信息

批准号：
9545804
负责人：
Hemant D Tagare
金额：
$ 33.04万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9545804
关键词：
Algorithms Anisotropy Biological Canada Cells China Collaborations Complex Computer software Crystallization Development Docking Educational workshop Electron Microscopy Europe European Feedback Goals Heterogeneity Image Internet Journals Length Letters Macromolecular Complexes Maps Mathematics Methods Modeling Modification Molecular Nature Noise Phase Price Process Proteins Published Comment Publishing Pythons Research Research Infrastructure Resolution Schedule Science Spain Speed Structure Techniques Testing Time Training United States National Academy of Sciences Variant Work base cryogenics data warehouse density design macromolecule mathematical theory open source parallel processing particle protein structure reconstruction scale up signal processing software development theories three dimensional structure tomography tool web interface

项目摘要

Cryogenic electron microscopy (cryo-EM) is now yielding atomic or near-atomic resolution structures for proteins and other biological macromolecular complexes via single particle reconstruction (SPR) and tomography. This comes at a price – cryo-EM structures are noisy and have to be filtered at the appropriate resolution before they can be interpreted. The problem is that particle heterogeneity, errors in image alignment, and the missing wedge in tomography cause the resolution to be non-uniform in the reconstructed density. A recent mathematical theory by the P.I. led to a definition of local resolution and to an algorithm for calculating the local resolution. Called, ResMap, this algorithm has been widely downloaded and is included (or will be included soon) in all widely-used cryo-EM packages such as RELION, EMAN, Xmipp (Scipion) and Frealign. This proposal seeks to substantially extend and harden ResMap. First, it seeks to scale up ResMap to deal with large maps. Second, it seeks to create a notion of local anisotropic resolution. Third, it seeks to create adaptive filters so that the density map can be filtered with a kernel whose size varies with local resolution. All of the developments are requested by current users of ResMap. They will be made available through new versions of ResMap which will be hardened by collaboration with users, package developers, the Protein Data Bank (PDB) and the European Research Strategic Infrastructure (ESRI). The PDB and ESRI will make ResMap available over the web.

低温电子显微镜（Cryo-EM）现在产生原子或接近原子分辨率的结构通过单个颗粒重建（SPR）和断层扫描。这是有代价的 - 冷冻EM结构是噪音，必须在适当的情况下过滤在可以解释之前解决。问题是粒子异质性，图像对齐中的错误，在断层扫描中缺失的楔形导致分辨率在重建密度中是不均匀的。一个 P.I.的最新数学理论导致了本地分辨率的定义和用于计算的算法本地分辨率。称为Resmap，此算法已被广泛下载并包括在内（或将是很快包括）在所有广泛使用的冷冻EM软件包中，例如Relion，Eman，Xmipp（Scipion）和Frealign。该提案旨在实质上扩展并硬化。首先，它试图扩展重新限制以进行交易带有大地图。其次，它试图创建局部各向异性分辨率的概念。第三，它试图创造自适应过滤器，以便可以用大小随局部分辨率而变化的内核过滤密度图。全部 Resmap的当前用户要求开发。它们将通过新的 Resmap的版本将通过与用户，包装开发人员，蛋白质数据的协作来硬化银行（PDB）和欧洲研究战略基础设施（ESRI）。 PDB和ESRI会做通过网络可用。