Simulating the unwinding of DNA - Method development, application and didactic dissemination.

Abstract

Understanding diseases related to DNA requires insight into the nature of DNA dynamics, specifically how the dynamics affects the equilibrium properties.

The mesoscopic Peyrard-Bishop-Dauxois model has been able to reproduce DNA denaturation curves obtained experimentally. We conducted the first quantitative study in which dynamical results from the PBD model were compared with experiments. We showed that contrary to previous findings, having the GC base pairs distributed evenly throughout the DNA chain does not always give the fastest possible denaturation. Although reproducing thermodynamic properties quite well, the PBD model overestimates denaturation rates by several orders of magnitude. Thus, we introduced an adaption of the PBD model to study the denaturation of hairpins which exhibited a more accurate description of the unzipping process for short sequences.

After this, the PBD model was used as a test case system to test two new path-generating moves in Replica Exchange Transition Interface Sampling (RETIS), stone skipping (SS) and web throwing (WT), which improved the speed of convergence by a factor 12.

At the end we conducted a didactical study in order to examine pedagogical aspects of how to teach best the complex mathematical algorithms that were used in this thesis using web-based exercises.

In particular, we examined if self-evaluation is a useful instrument in these types of exercises.