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Mechanisms of Protein Search for Targets on DNA: Theoretical Insights

Institute for Medical Engineering and Science, Massachusetts Institute of Technology; Cambridge, MA 02142, USA
Department of Biomedical Engineering and System Biology Institute, Yale University West Haven, New Haven, CT 06516, USA
Department of Chemistry, Department of Chemical and Biomolecular Engineering, and Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA
Author to whom correspondence should be addressed.
Academic Editor: Junji Iwahara
Molecules 2018, 23(9), 2106;
Received: 30 July 2018 / Revised: 13 August 2018 / Accepted: 17 August 2018 / Published: 22 August 2018
(This article belongs to the Special Issue Protein-DNA Interactions: From Biophysics to Genomics)
Protein-DNA interactions are critical for the successful functioning of all natural systems. The key role in these interactions is played by processes of protein search for specific sites on DNA. Although it has been studied for many years, only recently microscopic aspects of these processes became more clear. In this work, we present a review on current theoretical understanding of the molecular mechanisms of the protein target search. A comprehensive discrete-state stochastic method to explain the dynamics of the protein search phenomena is introduced and explained. Our theoretical approach utilizes a first-passage analysis and it takes into account the most relevant physical-chemical processes. It is able to describe many fascinating features of the protein search, including unusually high effective association rates, high selectivity and specificity, and the robustness in the presence of crowders and sequence heterogeneity. View Full-Text
Keywords: protein-DNA interactions; stochastic models; first-passage processes protein-DNA interactions; stochastic models; first-passage processes
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Shvets, A.A.; Kochugaeva, M.P.; Kolomeisky, A.B. Mechanisms of Protein Search for Targets on DNA: Theoretical Insights. Molecules 2018, 23, 2106.

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