THE PROBABILITY OF THE OCCURRENCE OF CIS -PEPTIDE UNITS IN PROTEINS AND POLYPEPTIDES

Abstract

The problem of the very rare occurrence of cis peptide units in proteins and polypeptides has been investigated and the probability of occurrence of such peptide units has been evaluated on the basis of conformational analysis. The higher intrinsic energy of the cis over the trans form is partially responsible for the rare occurrence of the former. We find that the conformational restrictions produced when a cis peptide unit occurs within an all-trans polypeptide chain provides an additional criterion. Conformational energy calculations, on a segment of two peptide units (called dipeptide for short) indicated that, relative to the trans-trans structure, the trans-cis or cis-trans structures can occur only to an extent of per cent. In the case of a tripeptide unit, calculations on the configurations trans-trans-trans and trans-cis-trans yielded for the non-prolyl and prolyl cis peptide units a probability of occurrence of about O· 1 per cent and 30 per cellt or higher, respectively. This explains the almost total absence of nonprolyl cis peptide units in polypeptide chains. On the other hand, the results indicate that the population of cis-Pro for the sequence X-Pro in globular proteins is likely to be appreciable and that these should be looked for. So also, in the non-prolyl case, cis peptide units are not forbidden, but may occur in rare cases, which should also be looked for.