1. Understanding the free energy landscapes and self-limiting assembly of DNA origamis using coarse-grained modelling
- Author
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Wong, Chak and Doye, Jonathan
- Abstract
Coarse-grained modelling of DNA nanostructures allows their structural, mechanical and thermodynamic properties to be characterised. In this thesis, we illustrated how coarse-grained modelling combined with umbrella sampling can be applied to compute the free energy landscapes of large DNA nanostructures, and how these landscapes can be used to characterise the self-limiting assembly of DNA origamis. We first described the mechanical deformation of DNA nanotubes by computing their free energy landscapes using distance-based order parameters. We analysed the behaviour of the nanotubes under different levels of bending stress and compared their behaviour to the worm-like chain model, revealing two regimes of bending depending on the localisation of the bending stress. We further demonstrated the computation of free energy landscapes on a mechanically bistable DNA origami. Interestingly, the landscape computed from simulations only shows one minimum, which is different from the bistable landscape inferred from experimental observations of ensembles of origamis. We decomposed the landscape into one component for each joint in the origami and discovered that only one such component showed bistability, which was masked by the other components and resulted in an overall landscape with a single minimum. We also examined the self-limiting assembly of DNA origamis. We studied a DNA origami that assembles with stress propagation through displacement accumulation. We characterised the structural properties of the origami monomer and its polymers, as well as the free energy landscapes of the monomer associated with the main stress accumulation mechanisms. We parameterised a simple one-dimensional model using the landscapes and ran Monte Carlo simulations to estimate the stress free energy of polymers as a function of their lengths. As an extension, we explored other possible DNA origami designs that could undergo self-limiting assembly through mechanisms other than displacement accumulation. In particular, we evaluated the use of curvature and twist accumulation to propagate stress in assemblies of DNA origamis.
- Published
- 2022