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Article Dans Une Revue Biophysical Journal Année : 2022

DeepTracer-ID: De novo protein identification from cryo-EM maps

Résumé

The recent revolution in cryo-electron microscopy (cryo-EM) has made it possible to determine macromolecular structures directly from cell extracts. However, identifying the correct protein from the cryo-EM map is still challenging and often needs additional sequence information from other techniques, such as tandem mass spectrometry and/or bioinformatics. Here, we present DeepTracer-ID, a server-based approach to identify the candidate protein in a user-provided organism de novo from a cryo-EM map, without the need for additional information. Our method first uses DeepTracer to generate a protein backbone model that best represents the cryo-EM map, and this model is then searched against the library of AlphaFold2 predictions for all proteins in the given organism. This method is highly accurate and robust for high-resolution cryo-EM maps: in all 13 experimental maps tested blindly, DeepTracer-ID identified the correct proteins as the top candidates. Eight of the maps were of known structures, while the other five unpublished maps were validated by prior protein annotation and careful inspection of the model refined into the map. The program also showed promising results for both homomeric and heteromeric protein complexes. This platform is possible because of the recent breakthroughs in large-scale three-dimensional protein structure prediction. Using this approach, we expect to not only detect the correct protein but also other isoforms or homologs that are structurally similar to the correct DeepTracer-ID: Protein identification

Dates et versions

pasteur-03747389 , version 1 (08-08-2022)

Identifiants

Citer

Luca Chang, Fengbin Wang, Kiernan Connolly, Hanze Meng, Zhangli Su, et al.. DeepTracer-ID: De novo protein identification from cryo-EM maps. Biophysical Journal, 2022, 121 (15), pp.2840-2848. ⟨10.1016/j.bpj.2022.06.025⟩. ⟨pasteur-03747389⟩

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