aIn this review, the protein-DNA interactions are discussed considering different perspectives, and the biological occurrence of this interaction is explained at atomic level. The evaluation of the amino acid-nucleotide recognition has been investigated analysing datasets for predicting the association preferences and the geometry that favours the interaction.Based on this knowledge, an affinity chromatographic method was developed also exploiting this biological favoured contact. In fact, the implementation of this technique brings the possibility to apply the concept of molecular interactions to the development of new purification methodologies. In addition, the integration of the information recovered by all the different perspectives can bring new insights about some biological mechanisms, though not totally clarified.