Electrostatics and flexibility in protein-DNA interactions

Abstract

CAP, cro, and lambda repressor represent a class of gene-regulatory proteins that bind specifically to DNA using a common bihelical motif. Examination of these structures suggest a possible mechanism for the binding of protein to DNA. The first step would be the formation of a non-specific protein-DNA complex energetically driven by the electrostatic interaction of asymetrically distributed charges on the surface of the protein that complement the charges on DNA. This attraction keeps the protein near the DNA, limiting diffusion to one dimension. As the protein slides, random thermal fluctuations twist and dip the protein over irregularities in the structure of the DNA. During these excursions, surface complementarity is sampled until the specific binding site is found. At this point the intervening solvent is displaced allowing the two molecules maximize their electrostatic and hydrogen bonding interactions.