Distance-based global analysis of consistent cis-bonds in protein backbones

Biological polypeptides are known to contain cis-linkage in their main chain as a minor but important feature. Such anomalous connection of amino acids has different structural and functional effects on proteins. Experimental evidence of cis-bonds in proteins is mainly obtained using X-ray crystallography and other methods in the field of structural biology. To date, extensive analyses have been carried out on the experimentally found cis-bonds using the Protein Data Bank entry bases and/or residue bases; however, their consistency in each protein has not been examined on a global scale. Data accumulation and advances in methodology enable the use of new approaches from a proteomic point of view. Here, we sought to describe a simple procedure for the detection and confirmation of cis-bonds from a set of experimental coordinates for a protein to discriminate this type of bond from isomerizable and/or misassigned bonds. The resulting set of consistent cis bonds provides unprecedented insights into the trend of "high cis content" proteins and the upper limit of consistent cis bonds per polypeptide length. Recognizing such limit would not only be important for a practical check of upcoming structures, but also for the design of novel protein folds beyond the evolutionally-acquired repertoire.