Kinetics of Protein-DNA Interactions: First-Passage Analysis

TL;DR

This paper introduces a new theoretical first-passage analysis method to analytically study the dynamics of protein-DNA interactions, accounting for sequence heterogeneity and multiple target sites.

Contribution

It presents a fully analytic approach to model protein-DNA interaction kinetics, advancing understanding of biological search processes.

Findings

Analytic description of protein search for DNA binding sites.

Insights into effects of DNA heterogeneity on search dynamics.

Analysis of multiple targets and traps in protein search processes.

Abstract

All living systems can function only far away from equilibrium, and for this reason chemical kinetic methods are critically important for uncovering the mechanisms of biological processes. Here we present a new theoretical method of investigating dynamics of protein-DNA interactions, which govern all major biological processes. It is based on a first-passage analysis of biochemical and biophysical transitions, and it provides a fully analytic description of the processes. Our approach is explained for the case of a single protein searching for a specific binding site on DNA. In addition, the application of the method to investigations of the effect of DNA sequence heterogeneity, and the role multiple targets and traps in the protein search dynamics are discussed.