Skip to content. | Skip to navigation

Personal tools

Sections
You are here: Home / Teams / Dynamics and Control of Biological Assemblies and Macromolecular Machines - J. Martin / R. Pellarin / Publications / Building Protein Atomic Models from Cryo-EM Density Maps and Residue Co-Evolution.

Building Protein Atomic Models from Cryo-EM Density Maps and Residue Co-Evolution.

Guillaume Bouvier, Benjamin Bardiaux, Riccardo Pellarin, Chiara Rapisarda, and Michael Nilges (2022)

Biomolecules, 12(9).

Electron cryo-microscopy (cryo-EM) has emerged as a powerful method by which toobtain three-dimensional (3D) structures of macromolecular complexes at atomic ornear-atomic resolution. However, de novo building of atomic models fromnear-atomic resolution (3-5 Å) cryo-EM density maps is a challenging task, inparticular because poorly resolved side-chain densities hamper sequenceassignment by automatic procedures at a lower resolution. Furthermore,segmentation of EM density maps into individual subunits remains a difficultproblem when the structure of the subunits is not known, or when significantconformational rearrangement occurs between the isolated and associated form ofthe subunits. To tackle these issues, we have developed a graph-based method tothread most of the C-α trace of the protein backbone into the EM density map. TheEM density is described as a weighted graph such that the resulting minimumspanning tree encompasses the high-density regions of the map. A pruningalgorithm cleans the tree and finds the most probable positions of the C-α atoms,by using side-chain density when available, as a collection of C-α tracefragments. By complementing experimental EM maps with contact predictions fromsequence co-evolutionary information, we demonstrate that this approach cancorrectly segment EM maps into individual subunits and assign amino acidsequences to backbone traces to generate atomic models.

 
automatic medline import

Document Actions