Background: This research was carried out to provide a summary of a series of bioinformatical observations between 2002 and 2012 concerning the structure of nucleic acids and codons, the interaction between codons and nucleic acids and the general concept of translation. Methods: Public databases and resources, together with assays to determine the free folding energies in various codon residues, were utilized during this study. Results: This study demonstrates that widely-held paradigms within the field of molecular biology should be modified. In particular, it suggests that codons developed in association with the encoded amino acids, and that wobble bases are not randomly chosen in synonymous codons, since these have well-defined roles in determining the structure of nucleic acids and their folding energies. Furthermore, the proteomic code determines that co-locating amino acids are preferentially encoded by complementary codons (at least at the 1st and 3rd codon positions), and structural information transfer between nucleic acids and proteins during translation requires direct contact between “dedicated” amino acids and their codons. In addition, this study highlights the fact that there is a tRNA cycle that allows the possibility of direct codon amino acid contact. Conclusions: These observations provide a more complete understanding of the redundant Genetic Code and the mechanism of protein folding. Furthermore, the proteomic code provides the first real possibility for scientists to design interacting peptides that have high affinity and specificity for target peptides, with the potential to accelerate the growth of affinity assays and the integration of large numbers of affinity tests into chips.