Browsing by Author "Shin, Jaeoh"

Now showing 1 - 5 of 5
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    DNA Looping and DNA Conformational Fluctuations Can Accelerate Protein Target Search
    (American Chemical Society, 2021) Felipe, Cayke; Shin, Jaeoh; Kolomeisky, Anatoly B.; Center for Theoretical Biological Physics
    Protein searching and binding to specific sites on DNA is a fundamentally important process that marks the beginning of all major cellular transformations. While the dynamics of protein–DNA interactions in in vitro settings is well investigated, the situation is much more complex for in vivo conditions because the DNA molecules in live cells are packed into chromosomal structures where they are undergoing strong dynamic and conformational fluctuations. In this work, we present a theoretical investigation on the role of DNA looping and DNA conformational fluctuations in the protein target search. It is based on a discrete-state stochastic analysis that allows for explicit calculations of dynamic properties, which is also supplemented by Monte Carlo computer simulations. It is found that for stronger nonspecific interactions between DNA and proteins the search occurs faster on the DNA looped conformation in comparison with the unlooped conformation, and the fastest search is observed when the loop is formed near the target site. It is also shown that DNA fluctuations between the looped and unlooped conformations influence the search dynamics, and this depends on the magnitude of conformational transition rates and on which conformation is more energetically stable. Physical–chemical arguments explaining these observations are presented. Our theoretical study suggests that the geometry and conformational changes in DNA are additional factors that might efficiently control the gene regulation processes.
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    Facilitation of DNA loop formation by protein–DNA non-specific interactions
    (Royal Society of Chemistry, 2019) Shin, Jaeoh; Kolomeisky, Anatoly B.; Center for Theoretical Biological Physics
    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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    How Pioneer Transcription Factors Search for Target Sites on Nucleosomal DNA
    (American Chemical Society, 2022) Felipe, Cayke; Shin, Jaeoh; Kolomeisky, Anatoly B.; Center for Theoretical Biological Physics
    All major biological processes start after protein molecules known as transcription factors detect specific regulatory sequences on DNA and initiate genetic expression by associating to them. But in eukaryotic cells, much of the DNA is covered by nucleosomes and other chromatin structures, preventing transcription factors from binding to their targets. At the same time, experimental studies show that there are several classes of proteins, called “pioneer transcription factors”, that are able to reach the targets on nucleosomal DNA; however, the underlying microscopic mechanisms remain not well understood. We propose a new theoretical approach that might explain how pioneer transcription factors can find their targets. It is argued that pioneer transcription factors might weaken the interactions between the DNA and nucleosome by substituting them with similar interactions between transcription factors and DNA. Using this idea, we develop a discrete-state stochastic model that allows for exact calculations of target search dynamics on nucleosomal DNA using first-passage probabilities approach. It is found that the target search on nuclesomal DNA for pioneer transcription factors might be significantly accelerated while the search is slower on naked DNA in comparison with normal transcription factors. Our theoretical predictions are supported by Monte Carlo computer simulations, and they also agree with available experimental observations.
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    Molecular search with conformational change: One-dimensional discrete-state stochastic model
    (AIP Publishing LLC, 2018) Shin, Jaeoh; Kolomeisky, Anatoly B.; Center for Theoretical Biological Physics
    Molecular search phenomena are observed in a variety of chemical and biological systems. During the search, the participating particles frequently move in complex inhomogeneous environments with random transitions between different dynamic modes. To understand the mechanisms of molecular search with alternating dynamics, we investigate the search dynamics with stochastic transitions between two conformations in a one-dimensional discrete-state stochastic model. It is explicitly analyzed using the first-passage time probability method to obtain a full dynamic description of the search process. A general dynamic phase diagram is developed. It is found that there are several dynamic regimes in the molecular search with conformational transitions, and they are determined by the relative values of the relevant length scales in the system. Theoretical predictions are fully supported by Monte Carlo computer simulations.