title: EM-fold: de novo atomic-detail protein structure determination from medium-resolution density maps.
abstract: Electron density maps of membrane proteins or large macromolecular complexes are frequently only determined at medium resolution between 4 Å and 10 Å, either by cryo-electron microscopy or X-ray crystallography. In these density maps, the general arrangement of secondary structure elements (SSEs) is revealed, whereas their directionality and connectivity remain elusive. We demonstrate that the topology of proteins with up to 250 amino acids can be determined from such density maps when combined with a computational protein folding protocol. Furthermore, we accurately reconstruct atomic detail in loop regions and amino acid side chains not visible in the experimental data. The EM-Fold algorithm assembles the SSEs de novo before atomic detail is added using Rosetta. In a benchmark of 27 proteins, the protocol consistently and reproducibly achieves models with root mean square deviation values <3 Å.
authors.affiliation: Department of Chemistry and Center for Structural Biology, Vanderbilt University, Nashville, TN 37212, USA.
authors.forename: Steffen
authors.initials: S
authors.lastname: Lindert
authors.forename: Nathan
authors.initials: N
authors.lastname: Alexander
authors.forename: Nils
authors.initials: N
authors.lastname: Wötzel
authors.forename: Mert
authors.initials: M
authors.lastname: Karakaş
authors.forename: Phoebe L
authors.initials: PL
authors.lastname: Stewart
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
mesh_terms: D000465:Algorithms; D020285:Cryoelectron Microscopy / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D046911:Macromolecular Substances / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods*; D011487:Protein Conformation; D017510:Protein Folding; D012984:Software
chemical_list: D046911:Macromolecular Substances; D008565:Membrane Proteins