Protein structure comparison is a central issue in structural bioinformatics. The standard dissimilarity measure for protein structures is the root mean square deviation (RMSD) of representative atom positions such as alpha-carbons. To evaluate the RMSD the structures under comparison must be superimposed optimally so as to minimize the RMSD. How to evaluate optimal fits becomes a matter of debate, if the structures contain regions which differ largely--a situation encountered in NMR ensembles and proteins undergoing large-scale conformational transitions.