6.2 Non-covalent bonding in site-specific binding

The affinity of a protein for DNA is determined in thermodynamic terms by the free energies of the individual components compared to the free energy of the DNA-protein complex. DNA binding proteins, which contain different binding motifs, demonstrate a wide range of thermodynamic strategies.

The affinity of a site-specific DNA binding protein for its specific DNA sequence is generally of the order of 10⁴−10⁷ times greater than its affinity for non-specific sequences. Stable protein–DNA interactions arise from the combination of non-covalent interactions that we have seen in other macromolecules: hydrogen bonding, electrostatic interactions, hydrophobic interactions and van der Waals forces. These interactions can occur between protein side-chain groups and either the DNA deoxyribose-phosphate backbone or the bases. There are many types of proteins that interact with DNA, both specifically and non-specifically. Below we will briefly consider examples of how each of these types of interaction occurs, to illustrate the principles involved.