How proteins search for their targets on DNA.

Abstract

It is known since the early days of molecular biology that proteins locate their specific targets on DNA up to two orders-of-magnitude faster than the Smolu- chowski three-dimensional (3D) diffusion rate. An accepted explanation of this fact is that proteins are nonspecifically adsorbed on DNA, and sliding along DNA provides for the faster one-dimensional (1D) search. We explicitly addressed the role of DNA conformation and the dispersion of nonspecific adsorption energies. We identified a wealth of new different scaling regimes and found that the maxi- mum on the rate-versus-ionic strength curve is asymmetric. We also studied the other facilitating mechanism termed intersegment trans- ferwhere proteins which have two DNA binding sites can transfer from one DNA segment to another without dissociation to water. We proposed a scaling the- ory which combines the effects of protein 3D diffusion, 1D sliding, intersegment transfer and DNA motion. A direct application of our work on target search problem is the kinetics of viral self-assembly. We show that due to the 1D sliding of capsid proteins on the unassembled chain of single-stranded RNA, the self-assembly is more than ten times faster than the case involving only three-dimensional diffusion. We further extended our theory to the macroscopic diffusion coefficient of proteins in a semi-dilute solution of DNA pieces and the effective conductivity of a composite made of well conducting nanowires suspended in some poor conducting medium.