Protein model refinement addresses these defects. Refinement aims at improving initial model qualities towards the accuracy of experimental structures in terms of global structure arrangement, local structure packing, and stereochemical correctness. Several methods have been proposed that address these tasks. Earlier methods primarily focused on the refinement of local structures by improving sidechain packing or hydrogen bond networks, whereas the global structure could only be refined slightly along with the local structure improvements. More recently, molecular dynamics (MD) simulations have been applied to improve global structure more substantially. MD simulations allow extensive sampling and refinement becomes possible when the force field is good enough to guide sampling to the native state at the lowest free energy. Moreover, ensemble-averaging has been found to be key to the success of MDbased structure refinement as the resulting models better resemble how experimental structures are obtained.