EM-fold: De novo folding of alpha-helical proteins guided by intermediate-resolution electron microscopy density maps.
In medium-resolution (7-10 A) cryo-electron microscopy (cryo-EM) density maps, alpha helices can be identified as density rods whereas beta-strand or loop regions are not as easily discerned. We are proposing a computational protein structure prediction algorithm "EM-Fold" that resolves the density rod connectivity ambiguity by placing predicted alpha helices into the density rods and adding missing backbone coordinates in loop regions. In a benchmark of 11 mainly alpha-helical proteins of known structure a native-like model is identified in eight cases (rmsd 3.9-7.9 A). The three failures can be attributed to inaccuracies in the secondary structure prediction step that precedes EM-Fold. EM-Fold has been applied to the approximately 6 A resolution cryo-EM density map of protein IIIa from human adenovirus. We report the first topological model for the alpha-helical 400 residue N-terminal region of protein IIIa. EM-Fold also has the potential to interpret medium-resolution density maps in X-ray crystallography.
Lindert
Steffen
S
Department of Chemistry, Vanderbilt University, Nashville, TN 37212, USA.
Staritzbichler
René
R
Wötzel
Nils
N
Karakaş
Mert
M
Stewart
Phoebe L
PL
Meiler
Jens
J
D000260:Adenoviruses, Human / Q000737:chemistry / Q000648:ultrastructure; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D019295:Computational Biology; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006801:Humans; D008854:Microscopy, Electron; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012372:ROC Curve; D012243:Rhodopsin / Q000737:chemistry / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D012984:Software
D011506:Proteins; C013110:metarhodopsins; D012243:Rhodopsin