  Intrinsically disordered proteins (IDPs) and multidomain proteins with
flexible linkers show a high level of structural heterogeneity and are best
described by ensembles consisting of multiple conformations with associated
thermodynamic weights. Determining conformational ensembles usually involves
integration of biophysical experiments and computational models. In this
review, we discuss current approaches to determining conformational ensembles
of IDPs and multidomain proteins, including the choice of biophysical
experiments, computational models used to sample protein conformations, models
to calculate experimental observables from protein structure, and methods to
refine ensembles against experimental data. We also provide examples of recent
applications of integrative conformational ensemble determination to study IDPs
and multidomain proteins and suggest future directions for research in the
field.
