Cylindrical Similarity Measurement for Helices in Medium-Resolution Cryo-Electron Microscopy Density Maps

Cryo-electron microscopy (cryo-EM) density maps at medium resolution (5-10 Å) reveal secondary structural features such as α-helices and β-sheets, but they lack the side chain details that would enable a direct structure determination. Among the more than 800 entries in the Electron Microscopy Data Bank (EMDB) of medium-resolution density maps that are associated with atomic models, a wide variety of similarities can be observed between maps and models. To validate such atomic models and to classify structural features, a local similarity criterion, the F₁ score, is proposed and evaluated in this study. The F₁ score is theoretically normalized to a range from zero to one, providing a local measure of cylindrical agreement between the density and atomic model of a helix. A systematic scan of 30,994 helices (among 3,247 protein chains modeled into medium-resolution density maps) reveals an actual range of observed F₁ scores from 0.171 to 0.848, suggesting that the cylindrical fit of the current data is well stratified by the proposed measure. The best (highest) F₁ scores tend to be associated with regions that exhibit high and spatially homogeneous local resolution (between 5 Å and 7.5 Å) in the helical density. The proposed F₁ scores can be used as a discriminative classifier for validation studies and as a ranking criterion for cryo-EM density features in databases.