Protein-induced DNA bending: the role of phosphate neutralisation

An important component of protein-nucleic acid interactions is the formatio n of salt bridges between cationic amino acid side chains and the anionic p hosphate groups of the nucleic acid. We have used molecular mechanics to st udy the energetic and conformational impact of such interactions. Firstly, crystallographic protein-nucleic acid complexes from the: Protein Data Bank were analysed in terms of DNA curvature and the presence of salt bridges. For complexes where the DNA is significantly bent, the contribution of salt bridges to this curvature was modelled by studying the effect of neutralis ing the appropriate phosphate groups. The number and the distribution of sa lt bridges vary widely for different DNA binding motifs and appear to have very different effects on DNA. In the case of homeodomain, bZIP and helix-l oop-helix proteins, salt bridges induce DNA bending, whereas for prokaryoti c helix-turn-helix proteins the number of salt bridges is much smaller and little bending is found. By analysing the components of the DNA deformation energy involved in protein binding we show that salt bridges consistently increase the flexibility of the DNA backbone.