EMatch: Discovery of high resolution structural homologues of protein domains in intermediate resolution cryo-EM maps

Cryo-EM has become an increasingly powerful technique for elucidating the structure, dynamics, and function of large flexible macromolecule assemblies that cannot be determined at atomic resolution. However, due to the relatively low resolution of cryo-EIM data, a major challenge is to identify components of complexes appearing in cryo-EM maps. Here, we describe EMatch, a novel integrated approach for recognizing structural homologues; of protein domains present in a 6-10 angstrom resolution cryo-EM map and constructing a quasi-atomic structural model of their assembly. The method is highly efficient and has been successfully validated on various simulated data. The strength of the method is demonstrated by a domain assembly of an experimental cryo-EM map of native GroEL at 6 angstrom resolution.