Most amino acids have a strong energetic preference for the trans peptide bond conformation due to steric hindrance, but proline's unusual structure stabilizes the cis form so that both isomers are populated under biologically relevant conditions.
Proline is unique among the natural amino acids in having a relatively small difference in free energy between the cis configuration of its peptide bond and the more common trans form.
The activation energy required to catalyse the isomerisation between cis and trans is relatively high: ~20kcal/mol (cf.
Unlike regular peptide bonds, the X-prolyl peptide bond will not adopt the intended conformation spontaneously, thus, the process of cis-trans isomerization can be the rate-limiting step in the process of protein folding.
Parvulin and human cytosolic FKBP are thought to catalyze their own folding processes.