Understanding the myriad protein-protein interactions required for cell function requires efficient leveraging of biophysical data to drive computational docking. The detailed insight into protein interfaces provided by isotope exchange endows this experimental technique with a unique importance for docking approaches. However, progress in coupling these methods is hindered by the inability to interpret the complex exchange patterns in relation to protein structure. A method to simulate protein isotope exchange patterns from docking outputs is described and its utility to guide the selection of native assemblies demonstrated. Unique signatures are generated for each docking pose, allowing high-throughput ranking of whole docking simulations by pairwise comparison to experimental outputs. Native assemblies are obtained using nothing but their simulated profiles as restraints and experimental difference data for individual proteins are sufficient to drive structure determination for the whole complex.