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Complex DNA topological structures, including polymer loops, are frequently observed in biological processes when protein molecules simultaneously bind to several distant sites on DNA. However, the molecular mechanisms of formation of these systems remain not well understood. Existing theoretical studies focus only on specific interactions between protein and DNA molecules at target sequences. However, the electrostatic origin of primary protein–DNA interactions suggests that interactions of proteins with all DNA segments should be considered. Here we theoretically investigate the role of non-specific interactions between protein and DNA molecules on the dynamics of loop formation. Our approach is based on analyzing a discrete-state stochastic model via a method of first-passage probabilities supplemented by Monte Carlo computer simulations. It is found that depending on a protein sliding length during the non-specific binding event three different dynamic regimes of the DNA loop formation might be observed. In addition, the loop formation time might be optimized by varying the protein sliding length, the size of the DNA molecule, and the position of the specific target sequences on DNA. Our results demonstrate the importance of non-specific protein–DNA interactions in the dynamics of DNA loop formations.
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Mechanisms of Protein Search for Targets on DNA: Theoretical Insights
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.
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- Award ID(s):
- 1664218
- PAR ID:
- 10094088
- Date Published:
- Journal Name:
- Molecules
- ISSN:
- 1420-3049
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/doi:10.3390/molecules23092106
