Document Type
Article
Original Publication Date
2011
Journal/Book/Conference Title
BMC Bioinformatics
Volume
12
DOI of Original Publication
10.1186/1471-2105-12-S10-S18
Date of Submission
August 2014
Abstract
Background
Proteins search along the DNA for targets, such as transcription initiation sequences, according to one-dimensional diffusion, which is interrupted by micro- and macro-hopping events and intersegmental transfers that occur under close packing conditions.
Results
A one-dimensional diffusion-reaction model in the form of difference-differential equations is proposed to analyze the nonequilibrium protein sliding kinetics along a segment of bacterial DNA. A renormalization approach is used to derive an expression for the mean first-passage time to arrive at sites downstream of the origin from the occupation probabilities given by the individual transport equations. Monte Carlo simulations are employed to assess the validity of the proposed approach, and all results are interpreted within the context of bacterial transcription.
Conclusions
Mean first-passage times decrease with increasing reaction rates, indicating that, on average, surviving proteins more rapidly locate downstream targets than their reaction-free counterparts, but at the price of increasing rarity. Two qualitatively different screening regimes are identified according to whether the search process operates under “small” or “large” values for the dissociation rate of the protein-DNA complex. Lower bounds are placed on the overall search time for varying reactive conditions. Good agreement with experimental estimates requires the reaction rate reside near the transition between both screening regimes, suggesting that biology balances a need for rapid searches against maximum exploration during each round of the sliding phase.
Rights
© 2011 Mayo et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Is Part Of
VCU Computer Science Publications
Comments
Originally found at http://dx.doi.org/10.1186/1471-2105-12-S10-S18