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Intrinsically disordered proteins are recognized to play key
biological roles, however current structural biology and simulation
techniques are often poorly suited to characterizing them. Experimental
methods such as Förster resonance energy transfer (FRET), nuclear
magnetic resonance (NMR) spectroscopy and small-angle X-ray scattering
(SAXS) can all yield useful information, but are averaged over a very
heterogeneous structural ensemble, making interpretation difficult.
Here, I illustrate how molecular simulation can be used as an aid in
determining a molecular model reflecting the structural and dynamic
properties observed in experiment. In particular, I will focus on the
recently discovered example of two intrinsically disordered proteins
which bind with 1:1 stoichiometry to form a complex with nanomolar
affinity mediated by the opposing charges of the molecules.
Coarse-grained molecular simulations with a simple empirical potential
are able to explain a range of FRET and NMR data for the complex.
Remarkably, they reveal that both proteins remain essentially completely
disordered when bound -- results which are backed up by independent
all-atom simulations of the same complex. This raises the question of
how frequent such fully disordered complexes may be in biology.