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Highlighted Reviews and Perspectives from Biophysical Journal

What is in the black box? – A perspective on software in cryoelectron microscopy

Suvrajit Maji and Joachim Frank

(Biophysical Journal (2021),

Cryoelectron microscopy currently dominates the biophysical study of molecular structure and is having a major impact throughout biophysics. Essential to the method is software that performs sophisticated computations to render electron density maps by using vast streams of noisy data. The Biophysical Perspective by Maji and Frank provides a lucid explanation of this process, presenting elementary shape transforms to illustrate the computational building blocks and summarizing the elementary operations. The authors emphasize the importance of transparency of the software used in this computation. Transparency ensures that users can follow the operations and understand how electron density maps are generated. The authors bemoan the current trend toward opaque software that conceals these operations from users and prevents them from gaining an intuitive grasp of the origins of an electron density map. The Perspective provides aspiring cryoelectron microscopists with a survey of currently available software packages, with an emphasis on the accessibility of their operation. This article emphasizes the importance of incorporating training in how software implements basic signal-processing operations, a point of considerable value in the education of structural biophysicists. Students should learn about the pitfalls of using software without having a clear grasp of the underlying computations, and the authors advance this goal very well. Readers of The Biophysicist with interests in cryoelectron microscopy are thus well advised to read this Perspective.

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