EM-fold: De novo folding of alpha-helical proteins guided by intermediate-resolution electron microscopy density maps.

Lindert S, Staritzbichler R, Wötzel N, Karakaş M, Stewart PL, Meiler J
Structure. 2009 17 (7): 990-1003

PMID: 19604479 · PMCID: PMC3760413 · DOI:10.1016/j.str.2009.06.001

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.

MeSH Terms (24)

Adenoviruses, Human Algorithms Amino Acid Sequence Animals Cattle Computational Biology Computer Simulation Cryoelectron Microscopy Crystallography, X-Ray Databases, Protein Humans Microscopy, Electron Models, Chemical Models, Molecular Molecular Sequence Data Monte Carlo Method Protein Conformation Protein Folding Proteins Protein Structure, Secondary Rhodopsin ROC Curve Sequence Homology, Amino Acid Software

Connections (2)

This publication is referenced by other Labnodes entities: