where d ij and d ij o are distances between Cα atoms of the i-th and j-th residues for an instantaneous conformation and the initial model, respectively. This restraint was applied to residue pairs with distances below 10 Å in the initial model and separated by more than three residues. For the distance-based flatbottom harmonic restraint potential, we used k 0 = 0.05 kcal/mol/Å 2 and b flat = 2 Å. This choice of values gave a comparable biasing strength compared to the Cartesian restraints. Second, we tested a combined restraint between Cartesian and distance restraints (Eq. 3).