Integration of cryo-EM with atomic and protein-protein interaction data

Cryoelectron microscopy (cryo-EM) is an increasingly popular method to elucidate the structures of macromolecular complexes. However, in many applications the resolution of cryo-EM densities is limited to the low or intermediate resolution regime, that is, (10Å)(-1) or worse. Therefore, unambiguous molecular interpretation of cryo-EM densities requires efficient use of additional information, such as atomic structures of related subunits and protein-protein interaction data. Here, we describe how information from different sources can be combined to determine the approximate molecular architecture of complexes. Molecular dynamics based flexible fitting protocols allow subsequent refinement of the atomistic models.