Exploring the limits of fold discrimination by structural alignment: A large scale benchmark using decoys of known fold

► Structure alignment methods are used to assign proteins to fold groups. ► The accuracy of this procedure is difficult to test as the definition of folds can be debated. ► By defining folds topologically and building decoys with defined fold the accuracy of fold assignments can be tested. ► Protein structure alignments decoys of different fold can be assigned a high significance, leading to errors in fold classification. ► This observation can be extended to comparisons between decoy models and real protein structures.