The role of DNA-protein salt bridges in molecular recognition: a model study

A theoretical study is presented of the influence of salt bridges between cationic side chains and DNA phosphates on DNA conformation and flexibility. The DNA sequence studied is that of the catabolite activator protein binding oligomer from the crystallized complex. The effect of salt bridges is modeled by neutralization of net phosphate charges for the groups involved in such interactions in the crystallized complex. Energy-optimized conformations are obtained by molecular mechanics using the JUMNA program. Base sequence dependence is studied by moving the phosphate neutralization pattern along the sequence and also by point mutations. Normal mode analysis is used to evaluate DNA flexibility. The results obtained show that the free oligomer is already precurved in the direction favored by the protein, and the effect of phosphate neutralization is principally to increase this curvature. This effect is, however, strongly sequence dependent. In addition, it is shown that oligomer flexibility cannot be explained by a simple superposition of the properties of successive dinucleotide steps, strong long-range coupling effects are observed. In all the cases examined, phosphate neutralization, however, leads to a reduction in oligomer flexibility.