Computational Methods for Single-Particle Electron Cryomicroscopy.

Computational Methods for Single-Particle Electron Cryomicroscopy.
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DOI:
10.1146/annurev-biodatasci-021020-093826
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发表时间:
2020-07
期刊:
Annual review of biomedical data science
影响因子:
--
通讯作者:
Sigworth FJ
Sigworth FJ
中科院分区:
其他
文献类型:
--
作者:
Singer A;Sigworth FJ

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单粒子电子冷冻显微镜(Cryo-EM)是一种越来越受欢迎的技术,用于在近原子分辨率下阐明蛋白质和其他具有生物意义的复合体的三维结构。这是一种不需要结晶的成像方法,可以捕捉分子的本征状态。在单粒子低温电子显微镜中,需要根据单个分子的噪声二维层析投影来确定三维分子结构,这些分子的取向和位置是未知的。高水平的噪声和未知的姿态参数是使重建成为一个具有挑战性的计算问题的两个关键因素。更具挑战性的是,当被成像的单个分子处于不同的构象状态时,结构可变性和灵活运动的推断。本文从统计推理、机器学习和信号处理等方面讨论了单粒子低温电子显微镜确定结构的计算方法及其指导原则,这些方法在许多其他数据科学应用中也发挥着重要作用。
Single-particle electron cryomicroscopy (cryo-EM) is an increasingly popular technique for elucidating the three-dimensional structure of proteins and other biologically significant complexes at near-atomic resolution. It is an imaging method that does not require crystallization and can capture molecules in their native states. In single-particle cryo-EM, the three-dimensional molecular structure needs to be determined from many noisy two-dimensional tomographic projections of individual molecules, whose orientations and positions are unknown. The high level of noise and the unknown pose parameters are two key elements that make reconstruction a challenging computational problem. Even more challenging is the inference of structural variability and flexible motions when the individual molecules being imaged are in different conformational states. This review discusses computational methods for structure determination by single-particle cryo-EM and their guiding principles from statistical inference, machine learning, and signal processing that also play a significant role in many other data science applications.
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