posted on 2020-03-11, 15:44authored byCristina Paissoni, Alexander Jussupow, Carlo Camilloni
Small-angle
X-ray scattering (SAXS) experiments provide low-resolution
but valuable information about the dynamics of biomolecular systems,
which could be ideally integrated into molecular dynamics (MD) simulations
to accurately determine conformational ensembles of flexible proteins.
The applicability of this strategy is hampered by the high computational
cost required to calculate scattering intensities from three-dimensional
structures. We previously presented a hybrid resolution method that
makes atomistic SAXS-restrained MD simulation feasible by adopting
a coarse-grained approach to efficiently back-calculate scattering
intensities; here, we extend this technique, applying it in the framework
of metainference with the aim to investigate the dynamical behavior
of flexible biomolecules. The efficacy of the method is assessed on
the K63-diubiquitin, showing that the inclusion of SAXS restraints
is effective in generating a reliable conformational ensemble, improving
the agreement with independent experimental data.