How Conformational Dynamics Influences the Protein Search for Targets on DNA

Abstract

Protein search and association to specific target sequences on DNA is essential for all fundamental biological processes. The detailed qualitative and quantitative mechanism of fast target finding is still unknown in spite of numerous experimental and theoretical efforts. Particularly, the role of protein conformational fluctuations in the search dynamics remains uncovered. We extend developed earlier theoretical method to analyze how the conformational dynamic affects the process of finding the specific targets on DNA. Our approach is based on discrete-state stochastic model that takes into account main physical-chemical processes. This allows us to evaluate explicitly the protein search for the targets on DNA at different conditions. Our calculations show that conformational fluctuations might strongly affect the protein search dynamics. We discuss the contribution of the shift in the conformational equilibrium in the target search kinetics. We utilized extensive Monte Carlo computer simulations to validate our theoretical predictions.