Refinement with the combined restraints appears to be an optimal choice of restraints. By beginning sampling with the Cartesian restraints before gradually switching to distance restraints, it allows sampling to benefit from both types of restraints. Sampled structures with the combined restraints cover the conformational space for both types of sampling (Figure ). The scoring function, RWplus, could then select better conformations among the sampled structures. As a result, it could achieve refinement comparable to or even better than the best results with either Cartesian or distance restraints (Figure and