Protein information content resides in rare peptide segments

Discovering the informational rule(s) underlying structure–function relationships in the protein language is at the core of biology. Current theories have proven inadequate to explain the origins of biological information such as that found in nucleotide and amino acid sequences. Here, we demonstrate that the information content of an amino acid motif correlates with the motif rarity. A structured analysis of the scientific literature supports the theory that rare pentapeptide words have higher significance than more common pentapeptides in biological cell ‘talk’. This study expands on our previous research showing that the immunological information contained in an amino acid sequence is inversely related to the sequence frequency in the host proteome.