Assessment of long-term molecular dynamics calculations with experimental information on protein shape from X-ray scattering – SOD1 as a case study

Predicting protein plasticity with molecular dynamics (MD) calculations requires experimental assessment. Using small-angle X-ray scattering (SAXS) we compare scattering profiles computed from MD structures with experimental profiles from Cu–Zn superoxide dismutase (SOD1) in its metal-loaded and metal-free form. Forty-nanosecond MD calculations provide a sizeable pool of conformational states yielding a neat agreement with experiments for the metal-loaded enzyme and an exploration of flexible polypeptide segments in the metal-free dimer. This flexibility leads to a discrepancy between SAXS and MD which can be resolved proficiently by partial protein metallation highlighting the potential of this approach for examining overall conformational protein dynamics.