Model-based local density sharpening of cryo-EM maps

Atomic models based on high-resolution density maps are the ultimate result of the cryo-EM structure determination process. Here, we introduce a general procedure for local sharpening of cryo-EM density maps based on prior knowledge of an atomic reference structure. The procedure optimizes contrast of cryo-EM densities by amplitude scaling against the radially averaged local falloff estimated from a windowed reference model. By testing the procedure using six cryo-EM structures of TRPV1, beta-galactosidase, gamma-secretase, ribosome-EF-Tu complex, 20S proteasome and RNA polymerase Ill, we illustrate how local sharpening can increase interpretability of density maps in particular in cases of resolution variation and facilitates model building and atomic model refinement.