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Improved Algorithms for Macromolecular Structure Determination by cyro-EM

冷冻电镜大分子结构测定的改进算法

基本信息

批准号：
9301017
负责人：
Amit Singer
金额：
$ 32.42万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9301017
关键词：
Algorithms Area Biological Biological Process Certification Classification Complex Computational algorithm Computer software Cryoelectron Microscopy Crystallization Data Data Set Detection Development Dimensions Drug Design Electron Microscope Electron Microscopy Electrons Exhibits Failure Freezing Goals Heterogeneity Hydration status Ice Image Individual Investigation Lead Linear Algebra Liquid substance Macromolecular Complexes Mathematics Methods Molecular Molecular Conformation Molecular Structure Motion Names Negative Staining Nitrogen Noise Output Particle Size Performance Population Positioning Attribute Preparation Process Proteins Research Resolution Resort Rotation Sampling Signal Transduction Specimen Statistical Data Interpretation Structure Techniques Temperature Thinness Universities Validation Variant X-Ray Crystallography base computer framework cost heuristics improved insight interest macromolecule mathematical analysis novel novel strategies open source particle polypeptide programs protein structure public health relevance reconstruction signal processing structural biology success theories three dimensional structure

项目摘要

DESCRIPTION (provided by applicant): Single-particle electron cryomicroscopy (cryo-EM) is a method for observing the three- dimensional structures of large macromolecules. In cryo-EM the experimental data consist of noisy, random projection images of macromolecular "particles", and the problem is finding the 3D structure which is consistent with these images. The proposal aims to develop and apply to experimental data novel algorithms for solving two difficult mathematical problems posed by this technique of structural biology. First, classical cryo-EM reconstruction techniques assume that the particles are identical. However, in many datasets this assumption does not hold. Some molecules of interest have more than one conformational state. These structural variations are of great interest to biologists, as they provide insight int the functioning of the molecule. The first area of investigation in this project is the development of algorithmic and mathematical framework for determining structures associated with heterogeneous particle populations. The proposed algorithm is not only faster than existing techniques but is also mathematically provable to reveal the different conformations if the number of images is sufficiently large. Second, a major limiting factor for present cryo-EM studies is the particle size. Images of small particles are often too noisy for existing methods to provide valid three-dimensional reconstructions; although the images contain structural information, the assignment of orientations to the individual particles is unreliable. The second area of investigation focuses on developing a radical new approach for reconstruction of small particles without the need for determining particle orientations.

描述（由申请人提供）：单粒子电子低温显微镜（cryo-EM）是一种观察大型大分子三维结构的方法。在低温电镜中，实验数据是由大分子“粒子”的噪声、随机投影图像组成的，问题是找到与这些图像一致的三维结构。该提案旨在开发并应用于实验数据的新算法来解决由结构生物学技术提出的两个困难的数学问题。首先，经典的低温电镜重建技术假设粒子是相同的。然而，在许多数据集中，这种假设并不成立。一些感兴趣的分子有不止一种构象态。生物学家对这些结构变化非常感兴趣，因为它们提供了对分子功能的深入了解。这个项目的第一个调查领域是开发

项目成果

期刊论文数量（37）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Multi-target Detection with an Arbitrary Spacing Distribution.

DOI：
10.1109/tsp.2020.2975943
发表时间：
2020
期刊：
IEEE transactions on signal processing : a publication of the IEEE Signal Processing Society
影响因子：
0
作者：
Lan TY;Bendory T;Boumal N;Singer A
通讯作者：
Singer A

Orientability and Diffusion Maps.

可定向性和扩散图。