Modeling DNA and DNA-protein interactions

Abstract : The first part of my thesis deals with the modelling of DNA denaturation. I first used a statistical model (Poland-Scheraga) to show that one can predict the final positions of the fragments during 2D electrophoresis assays with a precision greater than experimental uncertainties. Then, I improved a dynamical model developed in our group by showing how its parameters can be varied to get predictions in better agreement with experimental results that were not addressed until now, like mechanical unzipping, the evolution of the critical temperature with sequence length, and temperature resolution. In the second part of my thesis I present a dynamical model for non-specific DNA-protein interactions. This model is based on a previously developed “bead-spring” model for DNA with elastic, bending and electrostatic interactions, while I chose to model protein-DNA interactions through electrostatic and excluded-volume forces. For the protein, I used two simple coarse-grained models: I first described the protein as a single bead and then improved this description by using a set of thirteen interconnected beads. I studied the properties of this model using a Brownian dynamics algorithm that takes hydrodynamic interactions into account, and obtained results that essentially agree with experiments. For example, I showed that the protein samples DNA by a combination of 3D diffusion in the buffer and 1D sliding along the DNA chain. I have also showed that this process, which is known as facilitated diffusion, cannot accelerate DNA sampling by proteins as much as it is sometimes believed to do.
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https://tel.archives-ouvertes.fr/tel-00542797
Contributor : Ana Maria Florescu <>
Submitted on : Monday, December 6, 2010 - 5:09:57 PM
Last modification on : Tuesday, September 11, 2018 - 11:00:02 AM
Long-term archiving on : Monday, March 7, 2011 - 3:55:32 AM

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  • HAL Id : tel-00542797, version 2

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Ana Maria Florescu. Modeling DNA and DNA-protein interactions. Biological Physics [physics.bio-ph]. Université Joseph-Fourier - Grenoble I, 2010. English. ⟨tel-00542797v2⟩

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