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 c ationic side chains and DNA phosphates on DNA conformation and flexibility. The DNA sequence studied is that of the the catabolite activator protein b inning oligomer from rile crystallized complex. The effect of salt bridges is modeled by neutralization of net phosphate charges for the groups involv ed in such interactions in the crystallized complex. Energy-optimized confo rmations are obtained by molecular mechanics using the JUMNA program. Base sequence dependence is studied by moving the phosphate neutralization patte rn along the sequence and also by point mutations. Normal mode analysis is used to evaluate DNA flexibility, The results obtained show that the free o ligomer is already precurved in the direction favored by the protein. and t he effect of phosphate neutralization is principally to increase this curva ture. This effect is, hok ei cp, strongly sequence dependent. In addition, it is shown that oligomer flexibility cannot be explained by a simple super position of the properties of successive dinucleotide steps, strong long-ra nge coupling effects are observed In all the cases examined phosphate neutr alization, however, lends to a reduction in oligomer flexibility. (C) 1999 John Wiley & Sons, Inc.