  The recent improvements in cryo-electron microscopy (cryo-EM) in the past few
years are now allowing to observe molecular complexes at atomic resolution. As
a consequence, numerous structures derived from cryo-EM are now available in
the Protein Data Bank. However, if for some complexes atomic resolution is
reached, this is not true for all. This is also the case in cryo-electron
tomography where the achievable resolution is still limited. Furthermore the
resolution in a cryo-EM map is not a constant, with often outer regions being
of lower resolution, possibly linked to conformational variability. Although
those low to medium resolution EM maps (or regions thereof) cannot directly
provide atomic structure of large molecular complexes, they provide valuable
information to model the individual components and their assembly into them.
Most approaches for this kind of modelling are performing rigid fitting of the
individual components into the EM density map. While this would appear an
obvious option, they ignore key aspects of molecular recognition, the
energetics and flexibility of the interfaces. Moreover, these often restricts
the modelling to a unique source of data, the EM density map. In this chapter,
we describe a protocol where an EM map is used as restraint in HADDOCK to guide
the modelling process.
