Browsing by Author "Kochugaeva, Maria"
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Item Dynamics of the Protein Search for Targets on DNA in the Presence of Traps(American Chemical Society, 2015) Lange, Martin; Kochugaeva, Maria; Kolomeisky, Anatoly B.; Center for Theoretical Biological PhysicsProtein search for specific binding sites on DNA is a fundamental biological phenomenon associated with the beginning of most major biological processes. It is frequently found that proteins find and recognize their specific targets quickly and efficiently despite the complex nature of protein–DNA interactions in living cells. Although significant experimental and theoretical efforts were made in recent years, the mechanisms of these processes remain not well-clarified. We present a theoretical study of the protein target search dynamics in the presence of semispecific binding sites which are viewed as traps. Our theoretical approach employs a discrete-state stochastic method that accounts for the most important physical and chemical processes in the system. It also leads to a full analytical description for all dynamic properties of the protein search. It is found that the presence of traps can significantly modify the protein search dynamics. This effect depends on the spatial positions of the targets and traps, on distances between them, on the average sliding length of the protein along the DNA, and on the total length of DNA. Theoretical predictions are discussed using simple physical–chemical arguments, and they are also validated with extensive Monte Carlo computer simulations.Item Protein search for multiple targets on DNA(AIP Publishing LLC., 2015) Lange, Martin; Kochugaeva, Maria; Kolomeisky, Anatoly B.; Center for Theoretical Biological PhysicsProtein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of experimental and theoretical investigations have been devoted to uncovering the molecular description of these phenomena, but many aspects of the mechanisms of protein search for the targets on DNA remain not well understood. One of the most intriguing problems is the role of multiple targets in protein search dynamics. Using a recently developed theoretical framework we analyze this question in detail. Our method is based on a discrete-state stochastic approach that takes into account most relevant physical-chemical processes and leads to fully analytical description of all dynamic properties. Specifically, systems with two and three targets have been explicitly investigated. It is found that multiple targets in most cases accelerate the search in comparison with a single target situation. However, the acceleration is not always proportional to the number of targets. Surprisingly, there are even situations when it takes longer to find one of the multiple targets in comparison with the single target. It depends on the spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Physical-chemical explanations of observed results are presented. Our predictions are compared with experimental observations as well as with results from a continuum theory for the protein search. Extensive Monte Carlo computer simulations fully support our theoretical calculations.Item Role of Static and Dynamic Obstacles in the Protein Search for Targets on DNA(America Chemical Society, 2015) Shvets, Alexey; Kochugaeva, Maria; Kolomeisky, Anatoly B.; Center for Theoretical Biological PhysicsProtein search for specific sequences on DNA marks the beginning of major biological processes. Experiments indicate that proteins find and recognize their targets quickly and efficiently. Because of the large number of experimental and theoretical investigations, there is a reasonable understanding of the protein search processes in purifiedᅠin vitroᅠsystems. However, the situation is much more complex in live cells where multiple biochemical and biophysical processes can interfere with the protein search dynamics. In this study, we develop a theoretical method that explores the effect of crowding on DNA chains during the protein search. More specifically, the role of static and dynamic obstacles is investigated. The method employs a discrete-state stochastic framework that accounts for most relevant physical and chemical processes in the system. Our approach also provides an analytical description for all dynamic properties. It is found that the presence of the obstacles can significantly modify the protein search dynamics. This effect depends on the size of the obstacles, on the spatial positions of the target and the obstacles, on the nature of the search regime, and on the dynamic nature of the obstacles. It is argued that the crowding on DNA can accelerate or slow down the protein search dynamics depending on these factors. A comparison with existing experimental and theoretical results is presented. Theoretical results are discussed using simple physical-chemical arguments, and they are also tested with extensive Monte Carlo computer simulations.Item Theoretical investigation of protein search for targets on DNA(2017-08-11) Kochugaeva, Maria; Kolomeisky, Anatoly BProtein-DNA interactions activate many biochemical transitions used by living systems for successful functioning. The starting point in this process is a protein search and recognition of specific target sequences on DNA among millions of non-specific sites. One of the most striking observations is the fact that some proteins can find their targets on DNA much faster than expected from 3D bulk diffusional estimates which follow from the famous theory developed by M.Smoluchovski. This phenomenon is known as facilitated diffusion. After extensive investigation via theoretical and experimental methods, it has been argued that the facilitated diffusion of proteins (also known as accelerated search) is possible due to combining 3D bulk motion with 1D sliding of non-specifically bound protein molecules along the DNA chain. The recent development of single-molecule techniques has allowed for direct visualization of protein sliding during its binding site search. Thus, although we now have a better understanding of protein search on DNA, there are still many unanswered questions and many features related to this complex biological phenomenon that are still not resolved at the molecular level. In this work we develop a theoretical method to explain the molecular picture behind these complex processes. Our approach is based on a discrete-state stochastic framework and utilizes a first-passage probability method that takes into account the most relevant physical-chemical processes. This allows us to explicitly evaluate the protein search for the targets on DNA for different conditions. Theoretical predictions are supported by Monte Carlo computer simulations, and obtained results are utilized for analysis of available experimental data.