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Automatic building of protein atomic models from cryo-EM density maps using residue co-evolution

Abstract : Electron cryo-microscopy (cryo-EM) has emerged as a powerful method to obtain three-dimensional (3D) structures of macromolecular complexes at atomic or near-atomic resolution. However, de novo building of atomic models from near-atomic resolution (3-5 Å) cryo-EM density maps is a challenging task, in particular since poorly resolved side-chain densities hamper sequence assignment by automatic procedures at a lower resolution. Furthermore, segmentation of EM density maps into individual subunits remains a difficult problem when no three-dimensional structures of these subunits exist, or when significant conformational changes occur between the isolated and complexed form of the subunits. To tackle these issues, we have developed a graph-based method to thread most of the C- α trace of the protein backbone into the EM density map. The EM density is described as a weighted graph such that the resulting minimum spanning tree encompasses the high-density regions of the map. A pruning algorithm cleans the tree and finds the most probable positions of the C- α atoms, using side-chain density when available, as a collection of C- α trace fragments. By complementing experimental EM maps with contact predictions from sequence co-evolutionary information, we demonstrate that our approach can correctly segment EM maps into individual subunits and assign amino acids sequence to backbone traces to generate full-atom models.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03063879
Contributor : Riccardo Pellarin <>
Submitted on : Monday, December 14, 2020 - 11:57:27 AM
Last modification on : Thursday, January 28, 2021 - 2:34:03 PM
Long-term archiving on: : Monday, March 15, 2021 - 7:11:45 PM

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Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

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Guillaume Bouvier, Benjamin Bardiaux, Riccardo Pellarin, Chiara Rapisarda, Michael Nilges. Automatic building of protein atomic models from cryo-EM density maps using residue co-evolution. 2020. ⟨pasteur-03063879⟩

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