Proteins that selectively bind to DNA play an active part in regulating transcription and separating double stranded DNA into single strands.
The binding protein finds its attachment point—a sequence of specific nucleotides—by a process of diffusing in the volume around the DNA and along the DNA strand itself. However, the ease with which the protein diffuses along the DNA until it finds the right sequence is surprising, given that the positively charged proteins should be attracted to the typically negatively charged DNA at any site along the strand.
Writing in Physical Review Letters, Vincent Dahirel and colleagues at Université Paris 6, France, demonstrate with simulations how geometry—namely, the relative shapes of the DNA and binding protein—affects the electrostatic force between the two molecules and the ease with which the protein can diffuse.
Dahirel et al. model the DNA as a solid cylinder and the protein as a variety of solid shapes with different curvatures: a sphere, a cylinder, and a cylinder or square block with a concave “nook.” Both molecules are assumed to be in an ionic solution.
What the group finds is that when the protein surface compliments that of the DNA, that is, it is convex with a similar curvature, there is a repulsive electrostatic force between the molecules at very short distances. The finding provides an explanation that reconciles the site specificity of the protein with its ability to diffuse easily: the protein is attracted to the vicinity of the DNA, but doesn’t adhere until it reaches the site with the right sequence, where hydrogen bonds overcome the short-range repulsive force. – Jessica Thomas