The success of refinement via MD is known to depend on protein size -smaller systems are easier to refine -and initial model quality -models that are two far or too close to the native state are more difficult to refine. This remains generally true with the improved protocol (Figures S10and S11), but as the new sampling protocol extended the range of refinable residues within a given target (Figure ) we found that refinement success was also generally extended to a wider range of targets with larger sizes and lower initial model quality. Especially, the use of multiple initial models was beneficial in this regard as it allowed a wider range of conformational states to be covered. As a result, the added ability to consistently refine residues with more than 200 residues (Figure and S11B) is a significant advance that is expected to expand the application of protein structure refinement towards high-resolution structure prediction.