  Achieving a comprehensive understanding of the behaviour of proteins is
greatly facilitated by the knowledge of their structures, thermodynamics and
dynamics. All this information can be provided in an effective manner in terms
of structural ensembles. A structural ensemble can be obtained by determining
the structures, populations and interconversion rates for all the main states
that a protein can occupy. To achieve this goal, integrative methods that
combine experimental and computational approaches provide powerful tools. Here
we focus on cryo-electron microscopy, which has become over recent years an
invaluable resource to bridge the gap from order to disorder in structural
biology. In this review, we provide a perspective of the current challenges and
opportunities in determining protein structural ensembles using integrative
approaches that can combine cryo-electron microscopy data with other available
sources of information, along with an overview of the tools available to the
community.
