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bioRxiv · 10.1101/2022.01.04.474974

Sequence assignment validation in cryo-EM models with checkMySequence

Chojnowski, G.
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Abstract

The availability of new AI-based protein structure prediction tools radically changed the way cryo-EM maps are interpreted, but it has not eliminated the challenges of map interpretation faced by a microscopist. Models will continue to be locally rebuilt and refined using interactive tools. This inevitably results in occasional errors, among which register-shifts remain one of the most difficult to identify and correct. Here we introduce checkMySequence; a fast, fully automated and parameter-free method for detecting register-shifts in protein models built into cryo-EM maps. We show that the method can assist model building in cases where poorer map resolution hinders visual interpretation. We also show that checkMySequence could have helped avoid a widely discussed sequence register error in a model of SARS-CoV-2 RNA-dependent RNA polymerase that was originally detected thanks to a visual residue-by-residue inspection by members of the structural biology community. SynopsisWe present a new method, checkMySequence, for fast and automated detection of register errors in protein models built into cryo-EM reconstructions.

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Chojnowski, G.. 2022-01-05. Sequence assignment validation in cryo-EM models with checkMySequence. https://doi.org/10.1101/2022.01.04.474974

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