The restraints were based on the restraint generation scheme of the original Rosetta method, which uses "bounded" restraints (Eq. 4) with σ = 1 Å, s = 0.5. Parameters of residue type-dependent contact distance upper bound, ub ij d , are taken from the original work. For structurally conserved regions, we used flat-bottom harmonic restraints (Eq. 2) instead of the "bounded" restraints. Conserved regions were defined as those where the root-mean-square difference of Cα-Cα distances between the selected models and the initial model was less than 2 Å. The flat-bottom harmonic restraints were used with k 0 = 0.25 kcal/mol/Å 2 and b flat = 1 Å. Extensive optimization was not needed for our purposes. Therefore, we hybridized structures with only ten populations over ten iterations rather than 50 populations over 50 iterations as in the original method. The starting populations at each iteration consisted of the initial model and selected models from the previous iteration. If there were insufficient models, they were replicated to fill up the starting population. Four out of ten hybridized models obtained at the end of the iterations were selected for the further refinement as alternative initial models.