Comparison of kinetic and dynamical models of DNA-protein interaction and facilitated diffusion

TL;DR

This paper compares kinetic and dynamical models of DNA-protein interaction, revealing that facilitated diffusion does not significantly accelerate target location and may even slow it down, challenging previous assumptions.

Contribution

It demonstrates that kinetic and dynamical models agree in predicting low efficiency of facilitated diffusion, providing a reconciled understanding of DNA-protein search mechanisms.

Findings

Both models support low facilitated diffusion efficiency.

Facilitated diffusion may slow down target search compared to 3D diffusion.

Results challenge the notion that facilitated diffusion greatly accelerates DNA targeting.

Abstract

It has long been asserted that proteins like transcription factors may locate their target in DNA sequences at rates that surpass by several orders of magnitude the three-dimensional diffusion limit thank to facilitated diffusion, that is the combination of one-dimensional (sliding along the DNA) and three-dimensional diffusion. This claim has been supported along the years by several mass action kinetic models, while the dynamical model we proposed recently (J. Chem. Phys. 130, 015103 (2009)) suggests that acceleration of targeting due to facilitated diffusion cannot be large. In order to solve this apparent contradiction, we performed additional simulations to compare the results obtained with our model to those obtained with the kinetic model of Klenin et al (Phys. Rev. Letters 96, 018104 (2006)). We show in this paper that the two models actually support each other and agree in predicting a low efficiency for facilitated diffusion. Extrapolation of these results to real systems even indicates that facilitated diffusion necessarily slows down the targeting process compared to three-dimensional diffusion.