Likelihood-based interactive local docking into cryo-EM maps in ChimeraX

Abstract

AbstractThe interpretation of cryo-EM maps often includes the docking of known or predicted structures of the components, which is particularly useful when the map resolution is worse than 4 Å. Although it can be effective to search the entire map to find the best placement of a component, the process can be slow when the maps are large. However, frequently there is a well-founded hypothesis about where particular components are located. In such cases, a local search using a map subvolume will be much faster because the search volume is smaller, and more sensitive because optimizing the search volume for the rotation search step enhances signal-to-noise. A Fourier-space likelihood-based local search approach, based on the previously-publishedem_placementsoftware, has been implemented in the newemplace_localprogram. Tests confirm that the local search approach enhances speed and sensitivity of the computations. An interactive graphical interface in the ChimeraX molecular graphics program provides a convenient way to set up and evaluate docking calculations, particularly in defining the part of the map into which the components should be placed.SynopsisLikelihood-based cryo-EM docking using ouremplace_localsoftware is faster and more sensitive than our related software,em_placement, when the approximate location of a component is known, and is available conveniently through a plugin to the ChimeraX visualization software.