The related concepts of protein dynamics, conformational ensembles and allostery are of-
ten difficult to study with molecular dynamics (MD) due to the timescales involved. We
present ExProSE (Exploration of Protein Structural Ensembles), a distance geometry-based
method that generates an ensemble of protein structures from two input structures. ExProSE
provides a unified framework for the exploration of protein structure and dynamics in a fast
and accessible way. Using a dataset of apo/holo pairs it is shown that existing coarse-grained
methods can often not span large conformational changes. For T4-lysozyme ExProSE is able
to generate ensembles that are more native-like than tCONCOORD and NMSim, and com-
parable to targeted MD. By adding additional constraints representing potential modulators,
ExProSE can predict allosteric sites. ExProSE ranks an allosteric pocket first or second for 27
out of 58 allosteric proteins, which is similar and complementary to existing methods. The
ExProSE source code is freely-available.