EMBuilder: A Template Matching-based Automatic Model-building Program for High-resolution Cryo-Electron Microscopy Maps.

The resolution of electron-potential maps in single-particle cryo-electron microscopy (cryoEM) is approaching atomic or near- atomic resolution. However, no program currently exists for de novo cryoEM model building at resolutions exceeding beyond 3.5 Å. Here, we present a program, EMBuilder, based on template matching, to generate cryoEM models at high resolution. The program identifies features in both secondary-structure and Cα stages. In the secondary structure stage, helices and strands are identified with pre-computed templates, and the voxel size of the entire map is then refined to account for microscopic magnification errors. The identified secondary structures are then extended from both ends in the Cα stage via a log-likelihood (LLK) target function, and if possible, the side chains are also assigned. This program can build models of large proteins (~1 MDa) in a reasonable amount of time (~1 day) and thus has the potential to greatly decrease the manual workload required for model building of high-resolution cryoEM maps.