美国洛斯阿拉莫斯国家实验室Thomas C. Terwilliger研究小组发现，通过密度图修正（density modification）可改善低温电子显微镜图谱 （cryo-EM maps)。 该研究于2020年8月17日发表于《自然—方法学》。

研究人员通过密度图修正可以优化单粒子低温电子显微镜图。该方法的理论基础类似于之前用于优化大分子X射线晶体学图的最大似然的密度修正。主要区别是在晶体学中的应用中傅里叶系数的误差绝大部分在相角，而cryo-EM中系数误差在相角和振幅中都有，同时cryo-EM可以提供有独立误差的半图。

这些差异形成了一种独特方法，可结合起始密度图信息和在密度图修正过程中获得的信息。密度图修正的过程被应用于104个数据集，成功改进了cyro-EM图和模型相关性，并提高了许多密度图上细节的可见性。该过程需要两个未掩盖的半图和有关已成像的大分子体积的序列文件或其他信息。

附：英文原文

Title: Improvement of cryo-EM maps by density modification

Author: Thomas C. Terwilliger, Steven J. Ludtke, Randy J. Read, Paul D. Adams, Pavel V. Afonine

Issue&Volume: 2020-08-17

Abstract: A density-modification procedure for improving maps from single-particle electron cryogenic microscopy (cryo-EM) is presented. The theoretical basis of the method is identical to that of maximum-likelihood density modification, previously used to improve maps from macromolecular X-ray crystallography. Key differences from applications in crystallography are that the errors in Fourier coefficients are largely in the phases in crystallography but in both phases and amplitudes in cryo-EM, and that half-maps with independent errors are available in cryo-EM. These differences lead to a distinct approach for combination of information from starting maps with information obtained in the density-modification process. The density-modification procedure was applied to a set of 104 datasets and improved map-model correlation and increased the visibility of details in many of the maps. The procedure requires two unmasked half-maps and a sequence file or other source of information on the volume of the macromolecule that has been imaged.

DOI: 10.1038/s41592-020-0914-9

Source: https://www.nature.com/articles/s41592-020-0914-9