Computational methods for analyzing conformational variability of macromolecular complexes from cryo-electron microscopy images

Computational methods for analyzing conformational variability of macromolecular complexes from cryo-electron microscopy images
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DOI:
10.1016/j.sbi.2016.12.011
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发表时间:
2017-04-01
影响因子:
6.8
通讯作者:
Jonic, Slavica
Jonic, Slavica
中科院分区:
生物学2区
文献类型:
--
作者:
Jonic, Slavica

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由于低温电子显微镜(cryo-EM)的最新技术进步,大分子复合物(病毒,核糖体等)的结构现在通常以近原子分辨率获得。此外,与其功能有关的复合物构象变化的研究正在取得进展。构象变异性分析通常是通过将图像分类为若干离散类来完成的,这些离散类被认为代表了样本中存在的所有构象状态。然而,当构象变化是连续的(样品包含连续的状态而不是一些离散的状态)时,离散的类别不能被有意义地定义。对于这样的情况下,最近开发了明确考虑连续构象变化的第一图像分析方法。本文重点介绍了低温电镜图像分析方法在构象变异性分析中的最新进展。
Thanks to latest technical advances in cryo-electron microscopy (cryo-EM), structures of macromolecular complexes (viruses, ribosomes, etc.) are now often obtained at near-atomic resolution. Also, studies of conformational changes of complexes, in connection with their function, are gaining ground. Conformational variability analysis is usually done by classifying images in a number of discrete classes supposedly representing all conformational states present in the specimen. However, discrete classes cannot be meaningfully defined when the conformational change is continuous (the specimen contains a continuum of states instead of a few discrete states). For such cases, first image analysis methods that explicitly consider continuous conformational changes were recently developed. The latest developments in cryo-EM image analysis methods for conformational variability analysis are the focus of this review.