Recognition of a DNA sequence by a protein is achieved by interface-coupled chemical and shape complementation. This complementation between the two molecules is clearly directional and is determined by the specific chemical contacts including mainly hydrogen bonds. Directionality is an instrumental property of hydrogen bonding as it influences molecular conformations, which also affects DNA-protein recognition. The prominent elements in the recognition of a particular DNA sequence by a protein are the hydrogen-bond donors and acceptors of the base pairs into the grooves of the DNA that must interact with complementary moieties of the protein partner. Protein side chains make most of the crucial contacts through bidentate and complex hydrogen-bonding interactions with DNA base edges hence conferring remarkable specificity.