How proteins search for their targets on DNA.

University of Minnesota Ph.D. dissertation. May 2008. Major: Physics. Advisor: Boris I. Shklovskii. 1 computer file (PDF); xi, 156 pages. Ill. (some col.)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