Protein sliding and hopping kinetics on DNA

TL;DR

This study uses Monte-Carlo simulations to dissect the sliding and hopping behaviors of proteins on DNA, revealing their distinct roles in diffusion and how various factors influence these mechanisms.

Contribution

It introduces a simulation-based approach to distinguish sliding and hopping kinetics of DNA-binding proteins, providing detailed insights into their diffusion dynamics.

Findings

Hundreds of slides and hops occur per diffusion trajectory.

Sliding dominates fast diffusion, hopping dominates slow diffusion.

Hopping kinetics are minimally affected by flow and salt concentration.

Abstract

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 simulations suggest the following results: (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.