The interactions of DNA with force are central to manifold fields of inquiry, including the de novo design of DNA nanostructures, the use of DNA to probe the principles of biological self-assembly, and the operation of cellular nanomachines. This work presents a survey of three distinct ways coarse-grained simulations can help characterize these interactions. A non-equilibrium energy landscape reconstruction technique is validated for use with the oxDNA model and a practical framework to guide future applications is established. A novel method for calculating entropic forces in DNA molecules is outlined and contrasted with existing, flawed approaches. Finally, a joint experimental-simulation study of large DNA origami nanostructures under force sheds light on design principles and, through vivid illustrations, their unfolding process. This text provides an accessible and exciting launching point for any student interested in the computational study of DNA mechanics and force interactions.

Nominated as an outstanding Ph.D. thesis by the Rudolf Peierls Centre for Theoretical Physics, University of Oxford, UK Presents a new method for calculating polymer entropic forces in coarse-grained models that can overcome pitfalls associated with commonly-used techniques Provides an informative introduction to the use of non-equilibrium analyses with coarse-grained biophysical models along with practical guidelines for applying them Maps the unfolding process of DNA origami nanostructures through detailed colour illustrations and analysis, shedding light on design principles

Autorentext

Megan holds a DPhil in Theoretical Physics from the University of Oxford, which she completed on a Rhodes Scholarship, in addition to a BSc in Astrophysics with first class honours and a Masters in Physics, both from the University of Alberta in Canada. Her multidiscplinary interests have yielded diverse publications, including physics education research papers and book reviews in Science magazine, and she has worked in both experimental and theoretical capacities. Megan is currently a Killam postdoctoral fellow at the University of Alberta, where she continues to use coarse-grained modelling to explore how biological systems exploit physical laws.

Inhalt
Introduction.- Simulation Methods.- Non-equilibrium bio-molecular unfolding under tension.- Force-induced unravelling of DNA origami.- Measuring internal forces in single-stranded DNA.- Conclusions.- Appendices.