9 research outputs found
Protein search for multiple targets on DNA
Protein-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
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.Comment: arXiv admin note: substantial text overlap with arXiv:1804.1011
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.National Science Foundation (U.S.) (Grant CHE-1664218)National Science Foundation (U.S.) (Grant PHY-1427654)Robert A. Welch Foundation (Grant C-1559
Optimal Length of Conformational Transition Region in Protein Search for Targets on DNA
The starting point of many fundamental
biological processes is
associated with protein molecules finding and recognizing specific
sites on DNA. However, despite a large number of experimental and
theoretical studies on protein search for targets on DNA, many molecular
aspects of underlying mechanisms are still not well understood. Experiments
show that proteins bound to DNA can switch between slow recognition
and fast search conformations. However, from a theoretical point of
view, such conformational transitions should slow down the protein
search for specific sites on DNA, in contrast to available experimental
observations. In addition, experiments indicate that the nucleotide
composition near the target site is more symmetrically homogeneous,
leading to stronger effective interactions between proteins and DNA
at these locations. However, as has been shown theoretically, this
should also make the search less efficient, which is not observed.
We propose a possible resolution of these problems by suggesting that
conformational transitions occur only within a segment around the
target where stronger interactions between proteins and DNA are observed.
Two theoretical methods, based on continuum and discrete-state stochastic
calculations, are developed, allowing us to obtain a comprehensive
dynamic description for the protein search process in this system.
The existence of an optimal length of the conformational transition
zone with the shortest mean search time is predicted