 Before the discovery of the first knotted protein, it was believed that the process of protein folding could not efficiently produce deep knots in protein backbones.Studies of the folding kinetics of a dimeric protein from "Haemophilus influenzae" have revealed that the folding of trefoil knot proteins may depend on proline isomerization.Computational algorithms have been developed to identify knotted protein structures, both to canvas the Protein Data Bank for previously undetected natural knots and to identify knots in protein structure predictions, where they are unlikely to accurately reproduce the native-state structure due to the rarity of knots in known proteins.