Protein sliding and hopping kinetics on DNA

DNA-binding proteins' alternating diffusion kinetics on and off nonspecific DNA (also called sliding and hopping respectively) are important for quantifying their target binding mechanisms. Using Monte-Carlo simulations, we deconvolved the sliding and hopping kinetics of GFP-LacI proteins on elongated DNA from their experimentally observed seconds-long diffusion trajectories. Our simulation results suggest the following: (1) In each diffusion trajectory, a protein makes on average hundreds of alternating slides and hops with a mean sliding time of several tens of ms; (2) sliding dominates the root mean square displacement of fast diffusion trajectories, whereas hopping dominates slow ones; (3) flow and variations in salt concentration have limited effects on hopping kinetics, while in vivo DNA configuration is not expected to influence sliding kinetics; furthermore, (4) the rate of occurrence for hops longer than 200 nm agrees with experimental data for EcoRV proteins. Experimental investigations of sliding proteins on DNA using SIMA [1] measurements on the timescale of milliseconds will be presented.[1]. DeCenzo, S. H., M. C. DeSantis, and Y. M. Wang. 2010 Optics Express 18(16):16628-39.