FragFit

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Motivation

An interactive tool for prediction, visualization and selection of missing segments in protein cryo-EM density maps.

FragFit is an interactive web service for guided modeling of missing segments such as loops or hinge regions into cryo-Electron Microscopy (cryo-EM) density maps [1]. Segments of up to 3-35 residues length can be effectively modeled into maps of different resolution. Fragments are taken from a pre-calculated and frequently updated database containing >1.000 million entries (Nov 2017) extracted from structural coordinates deposited in the PDB [2]. A fast hierarchical search algorithm (FragSearch [3]) selects up to 100 suitable fragments by using sequence similarity and geometrical fitting as evaluation criteria. The found fragments are then re-ranked by their cross-correlation to the user provided cryo-EM density map. To minimize calculation time and to reduce false positive predictions, the provided map is preprocessed.

Remodeling of protein segments guided by cryo-EM density maps

Especially flexible regions are badly resolved. FragFit provides the possibility to remodel those regions, presenting a possible conformational space ranked according to its fit to the density.

Visualization

Integration of the NGL viewer [4], a molecular viewer based on WebGL, allows visualization and interactive selection of a loop from a list of 100 suitable candidates. A color code is provided to indicate clashes or other relevant criteria to promote an individual choice of the most suitable loop. By inspection of the best 5 fitted fragments, prediction quality is enhanced [1].

Results

The fragments are provided for visual inspection and can be selected from the sortable result table. A selected loop inserted into the user provided protein can be downloaded. In addition, all 100 loop candidates can be downloaded for further analyses.