Finally, on a more philosophical note, the use of multiple alternative initial models raises the question of what exactly should be considered structure refinement. Strictly speaking, the classical idea of refinement is to take a given model and improve its accuracy, mostly via orthogonal approaches to how the initial model was generated. We believe that our proposed protocol of generating alternative initial models via hybridization using other structural templates still falls into such a framework as the initial model "drives" the hybridization and is always included in all of the refinement runs. However, one could also view the approach taken by us as a refinement protocol variant where conformational sampling from the initial model is effectively guided by alternative models in order to more effectively restrain conformational space to plausible (sub-)structures. While we did not exactly implement such a protocol here one could imagine a variety of such sampling protocols to fully address the still unresolved challenge of efficiently navigating an extremely high-dimensional landscape with significant kinetic barriers hindering progress towards finding the native state.