PFfit: Fitting Atomic Structures in 3D EM

Motivation. We develop a new generalized framework for fitting crystal structures into density maps. The framework includes three new scoring functions that quantify the goodness of fit between the crystal structure and density map: (A) the scattering potential score, which is based on using a more realistic representation of the input crystal structure in terms of the density map, (B) the non-uniform exterior penalty, which efficiently penalizes atoms outside a certain isocontour of the target density map, and (C) the skeleton-secondary structure score, which correlates the skeleton of the density map with secondary structural elements in the crystal structure. The framework also includes a search scheme based on non-uniform correlations over the space of rotations SO(3), and a reranking stage that improves confidence in fitting results obtained during the initial search stage. Results. We show that (A) The scattering potential performs better than the Gaussian blurring scheme currently used by a majority of existing fitting techniques, (B) the non-uniform exterior penalty, combined with the search scheme, provides a very fast estimate of the fitting pose, (C) the skeleton-secondary structure score provides an estimate of the goodness of fit when the resolution of the density map is sufficiently high, and (D) the search scheme has unique sampling properties that combine the best features of existing approaches. Availability. PFfit is available though our website.