Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-7910 Wissenschaftlicher Artikel Metzler, Ralf; Bauer, Maximilian; Rasmussen, Emil S.; Lomholt, Michael A. Real sequence effects on the search dynamics of transcription factors on DNA Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs. London Nature Publishing Group 2015 Scientific Reports 5 10072 10.1038/srep10072 Institut für Physik und Astronomie OPUS4-7941 misc Metzler, Ralf; Bauer, Maximilian; Rasmussen, Emil S.; Lomholt, Michael A. Real sequence effects on the search dynamics of transcription factors on DNA Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs. 2015 urn:nbn:de:kobv:517-opus4-79411 Institut für Physik und Astronomie OPUS4-35261 Wissenschaftlicher Artikel Bauer, Maximilian; Metzler, Ralf In vivo facilitated diffusion model Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model. San Fransisco PLoS 2013 8 PLoS one 8 1 10.1371/journal.pone.0053956 Institut für Physik und Astronomie OPUS4-37545 Wissenschaftlicher Artikel Godec, Aljaz; Bauer, Maximilian; Metzler, Ralf Collective dynamics effect transient subdiffusion of inert tracers in flexible gel networks Based on extensive Brownian dynamics simulations we study the thermal motion of a tracer bead in a cross-linked, flexible gel in the limit when the tracer particle size is comparable to or even larger than the equilibrium mesh size of the gel. The analysis of long individual trajectories of the tracer demonstrates the existence of pronounced transient anomalous diffusion. From the time averaged mean squared displacement and the time averaged van Hove correlation functions we elucidate the many-body origin of the non-Brownian tracer bead dynamics. Our results shed new light onto the ongoing debate over the physical origin of steric tracer interactions with structured environments. Bristol IOP Publ. Ltd. 2014 13 New journal of physics : the open-access journal for physics 16 10.1088/1367-2630/16/9/092002 Institut für Physik und Astronomie OPUS4-38309 Wissenschaftlicher Artikel Bauer, Maximilian; Godec, Aljaz; Metzler, Ralf Diffusion of finite-size particles in two-dimensional channels with random wall configurations Diffusion of chemicals or tracer molecules through complex systems containing irregularly shaped channels is important in many applications. Most theoretical studies based on the famed Fick-Jacobs equation focus on the idealised case of infinitely small particles and reflecting boundaries. In this study we use numerical simulations to consider the transport of finite-size particles through asymmetrical two-dimensional channels. Additionally, we examine transient binding of the molecules to the channel walls by applying sticky boundary conditions. We consider an ensemble of particles diffusing in independent channels, which are characterised by common structural parameters. We compare our results for the long-time effective diffusion coefficient with a recent theoretical formula obtained by Dagdug and Pineda Cambridge Royal Society of Chemistry 2014 11 Physical chemistry, chemical physics : a journal of European Chemical Societies 16 13 6118 6128 10.1039/c3cp55160a Institut für Chemie OPUS4-35899 Wissenschaftlicher Artikel Bauer, Maximilian; Metzler, Ralf Generalized facilitated diffusion model for DNA-binding proteins with search and recognition states Transcription factors (TFs) such as the lac repressor find their target sequence on DNA at remarkably high rates. In the established Berg-von Hippel model for this search process, the TF alternates between three-dimensional diffusion in the bulk solution and one-dimensional sliding along the DNA chain. To overcome the so-called speed-stability paradox, in similar models the TF was considered as being present in two conformations (search state and recognition state) between which it switches stochastically. Combining both the facilitated diffusion model and alternating states, we obtain a generalized model. We explicitly treat bulk excursions for rodlike chains arranged in parallel and consider a simplified model for coiled DNA. Compared to previously considered facilitated diffusion models, corresponding to limiting cases of our generalized model, we surprisingly find a reduced target search rate. Moreover, at optimal conditions there is no longer an equipartition between the time spent by the protein on and off the DNA chain. Cambridge Cell Press 2012 10 Biophysical journal 102 10 2321 2330 10.1016/j.bpj.2012.04.008 Institut für Physik und Astronomie OPUS4-38756 Wissenschaftlicher Artikel Bauer, Maximilian; Rasmussen, Emil S.; Lomholt, Michael A.; Metzler, Ralf Real sequence effects on the search dynamics of transcription factors on DNA Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs. London Nature Publ. Group 2015 13 Scientific reports 5 10.1038/srep10072 Institut für Physik und Astronomie OPUS4-7619 misc Bauer, Maximilian; Godec, Aljaž; Metzler, Ralf Diffusion of finite-size particles in two-dimensional channels with random wall configurations Diffusion of chemicals or tracer molecules through complex systems containing irregularly shaped channels is important in many applications. Most theoretical studies based on the famed Fick-Jacobs equation focus on the idealised case of infinitely small particles and reflecting boundaries. In this study we use numerical simulations to consider the transport of finite-size particles through asymmetrical two-dimensional channels. Additionally, we examine transient binding of the molecules to the channel walls by applying sticky boundary conditions. We consider an ensemble of particles diffusing in independent channels, which are characterised by common structural parameters. We compare our results for the long-time effective diffusion coefficient with a recent theoretical formula obtained by Dagdug and Pineda [J. Chem. Phys., 2012, 137, 024107]. 2014 urn:nbn:de:kobv:517-opus4-76199 Institut für Physik und Astronomie OPUS4-7618 Wissenschaftlicher Artikel Bauer, Maximilian; Godec, Aljaž; Metzler, Ralf Diffusion of finite-size particles in two-dimensional channels with random wall configurations Diffusion of chemicals or tracer molecules through complex systems containing irregularly shaped channels is important in many applications. Most theoretical studies based on the famed Fick-Jacobs equation focus on the idealised case of infinitely small particles and reflecting boundaries. In this study we use numerical simulations to consider the transport of finite-size particles through asymmetrical two-dimensional channels. Additionally, we examine transient binding of the molecules to the channel walls by applying sticky boundary conditions. We consider an ensemble of particles diffusing in independent channels, which are characterised by common structural parameters. We compare our results for the long-time effective diffusion coefficient with a recent theoretical formula obtained by Dagdug and Pineda [J. Chem. Phys., 2012, 137, 024107]. Cambridge RSC Publications 2014 10 Physical chemistry, chemical physics : PCCP ; a journal of European chemical societies 16 13 6118 6128 10.1039/C3CP55160A Institut für Physik und Astronomie