Comprehensive Local Resolution Analysis for Cryo-EM

冷冻电镜的综合局部分辨率分析

• 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
• 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

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）现在产生原子或近原子分辨率结构， 蛋白质和其他生物大分子复合物通过单粒子重建（SPR）， 断层扫描这是有代价的-冷冻EM结构是嘈杂的，必须在适当的频率下过滤。 在他们被解释之前。问题是粒子的不均匀性，图像对齐的错误， 并且断层摄影中缺失的楔形导致重建密度的分辨率不均匀。一 P.I.最近提出的数学理论导致了局部分辨率的定义和计算算法 地方决议。这个算法被称为ResMap，已经被广泛下载，并被包含在（或将被包含在） 包括很快）在所有广泛使用的cryo-EM包，如RELION，EMAN，XMIPP（Scipion）和Frealign。 该提案旨在大幅扩展和强化ResMap。首先，它寻求扩大ResMap的规模， 大地图。其次，它试图创建一个局部各向异性分辨率的概念。第三，它试图创造 自适应滤波器，使得可以利用大小随局部分辨率而变化的核对密度图进行滤波。所有 ResMap的当前用户要求进行开发。它们将通过新的 ResMap版本将通过与用户，软件包开发人员，蛋白质数据 欧洲研究战略基础设施（European Research Strategic Infrastructure，ESRI）。PDB和ESRI将使 ResMap可在网络上使用。