Abstract
This work seeks to remedy two deficiencies in the current nucleic acid nanotechnology software environment: the lack of both a fast and user-friendly visualization tool and a standard for ...structural analyses of simulated systems. We introduce here oxView, a web browser-based visualizer that can load structures with over 1 million nucleotides, create videos from simulation trajectories, and allow users to perform basic edits to DNA and RNA designs. We additionally introduce open-source software tools for extracting common structural parameters to characterize large DNA/RNA nanostructures simulated using the coarse-grained modeling tool, oxDNA, which has grown in popularity in recent years and is frequently used to prototype new nucleic acid nanostructural designs, model biophysics of DNA/RNA processes, and rationalize experimental results. The newly introduced software tools facilitate the computational characterization of DNA/RNA designs by providing multiple analysis scripts, including mean structures and structure flexibility characterization, hydrogen bond fraying, and interduplex angles. The output of these tools can be loaded into oxView, allowing users to interact with the simulated structure in a 3D graphical environment and modify the structures to achieve the required properties. We demonstrate these newly developed tools by applying them to design and analysis of a range of DNA/RNA nanostructures.
The design space for self-assembled multicomponent objects ranges from a solution in which every building block is unique to one with the minimum number of distinct building blocks that unambiguously ...define the target structure. We develop a pipeline to explore the design spaces for a set of structures of various sizes and complexities. To understand the implications of the different solutions, we analyze their assembly dynamics using patchy particle simulations and study the influence of the number of distinct building blocks, and the angular and spatial tolerances on their interactions, on the kinetics and yield of the target assembly. We show that the resource-saving solution with a minimum number of distinct blocks can often assemble just as well (or faster) than designs where each building block is unique. We further use our methods to design multifarious structures, where building blocks are shared between different target structures. Finally, we use coarse-grained DNA simulations to investigate the realization of multicomponent shapes using DNA nanostructures as building blocks.
As nucleic acid nanostructures grow larger and more complex, new tools and methods are needed to facilitate their design. DNA origami structures, for example, are limited by the lengths of their ...scaffolds but larger assemblies can be bound together by interactions between multiple components. This thesis presents two projects, each approaching the design of such modular structures at a different level of abstraction. Project 1 presents the polycube self-assembly model, where building blocks assemble stochastically using bindings between complementary patches. The assembly of both 2D polyominoes, as well as 3D polycubes, is considered. First, the mapping between input rules (defining the set of available species) and output shapes is investigated, revealing a clear bias toward low--complexity structures. Frequent shapes also tend to be highly modular and symmetric. Secondly, the reversed mapping is explored, presenting a method to find the minimal rule that assembles a specified output shape. Differences in assembly kinetics between possible solutions are investigated using patchy particle simulations, showing that minimal rules can assemble as well as fully addressable rules. Project 2 presents a more detailed approach to the design of modular structures and individual modules: the oxView toolkit for the design, analysis, and visualisation of DNA, RNA and protein nanostructures. While many other design tools exist, oxView makes it easy to import and connect their designs into complete assemblies. Furthermore, oxView allows for free-form editing and rigid-body manipulation. Designs can then be interactively simulated using the oxDNA model, providing a more intuitive understanding of the resulting dynamics. In conclusion, the design of self-assembling nucleic acid nanostructures has been investigated on both an abstract and a more detailed level. The presented projects have resulted in tools and methods for creating, simulating and analysing modular structures with minimal complexity, potentially containing building blocks created in multiple design software.
This work proposes an automated workflow using digital twinning for multi-domain environmental performance analysis of urban developments. Digital twins can potentially provide a common basis for ...multi-domain simulations and help overcome data availability and interoperability issues. The proposed workflow consists of five steps: (1) creating a procedural urban 3D model, (2) generating design alternatives parametrically, (3) exporting the context and each design alternative to each simulation tool, (4) running simulations for wind comfort, energy demand, and noise for each design alternative, and (5) combining and visualizing the simulation results using the digital twin. The workflow was applied to a neighbourhood in Sweden, the resultsreveal significant reduction in manual work when applying multiple simulation software for different domains. This is one step forward in streamlining the workflow for urban analysis, crucial for multi-domain optimization. In the future, further domains and simulation tools can be added to the workflow.
The design space for a self-assembled multicomponent objects ranges from a solution in which every building block is unique to one with the minimum number of distinct building blocks that ...unambiguously define the target structure. Using a novel pipeline, we explore the design spaces for a set of structures of various sizes and complexities. To understand the implications of the different solutions, we analyse their assembly dynamics using patchy particle simulations and study the influence of the number of distinct building blocks and the angular and spatial tolerances on their interactions on the kinetics and yield of the target assembly. We show that the resource-saving solution with minimum number of distinct blocks can often assemble just as well (or faster) than designs where each building block is unique. We further use our methods to design multifarious structures, where building blocks are shared between different target structures. Finally, we use coarse-grained DNA simulations to investigate the realisation of multicomponent shapes using DNA nanostructures as building blocks.
Ruptured liver Le, An Chau Maria; Bohlin, Tonje; Grønvold, Lars ...
Tidsskrift for den Norske Lægeforening,
05/2023, Letnik:
143, Številka:
8
Journal Article
PDF
