Kinetics and thermodynamics of unfolding processes in DNA molecules with several conformational states: theory and experiments

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Title: Kinetics and thermodynamics of unfolding processes in DNA molecules with several conformational states: theory and experiments
Authors: Nostheide, Sandra
Thesis advisor: Prof. Dr. Philipp Maa√ü
Thesis referee: Prof. Dr. Jochen Gemmer
Abstract: The modelling of single-molecule experiments is of vital interest to gain new insights into processes which were hitherto not accessible by measurements performed on bulk systems. In the first part of this thesis, the kinetics of a triple-branch DNA molecule with four conformational states is investigated by employing pulling experiments with optical tweezers and theoretical modelling. Probability distributions of first rupture forces, which are calculated by applying transition rate theory to a free energy model, show good agreement with experimental findings. Permanently frayed molecules could be identified by analysing the number of opening base pairs in force jumps. In the second part of the thesis, DNA hairpin molecules with periodic base sequences are studied. Their unfolding kinetics allows an analytical treatment, because they exhibit a regular coarse-grained free energy landscape as a function of the number of opened base pairs. A procedure is developed for determining all relevant parameters of the landscape, which relies on probabilities that can be easily sampled from the unfolding trajectories. By means of Monte Carlo simulations it is shown that already 300 trajectories, as typically measured in single-molecule experiments, provide faithful results for the energetic parameters. The approach in particular opens a new access to improve loop contributions in the free energy landscape. In the third part of the thesis, a simulation method is developed for modelling the unfolding kinetics of DNA molecules with arbitrary base sequences. The method is validated against experimental data for five DNA hairpin molecules with different length of the end-loop. Applications of the method enable one, among others, to improve the parameter determination in functional forms suggested for the tail behaviour of work distributions. Such work distributions enter detailed and integral fluctuation theorems, which are useful for estimating free energy differences between folded and unfolded states from nonequilibrium measurements.
Subject Keywords: Single-molecule experiments; DNA unfolding; biophysics; biomolecules; statistical physics; nonequilibrium kinetics; free energy landscape; Jarzynski estimator; free energy difference; work distribution; Monte Carlo simulation
Issue Date: 15-Oct-2014
License name: Namensnennung-NichtKommerziell-KeineBearbeitung 3.0 Unported
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Type of publication: Dissertation oder Habilitation [doctoralThesis]
Appears in Collections:FB04 - E-Dissertationen

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