Algorithmic Design of Biomolecular Nanostructures

Thumbnail Image
Journal Title
Journal ISSN
Volume Title
School of Science | Doctoral thesis (article-based) | Defence date: 2018-11-16
Degree programme
83 + app. 89
Aalto University publication series DOCTORAL DISSERTATIONS, 219/2018
Biomolecular nanotechnology, a field where biomolecules such as DNA and RNA are used as programmable nanoscale construction materials, is emerging as a breakthrough technology with promising applications in nanomedicine, materials science and biophysical research. To accelerate the developments in nucleic acid nanotechnology, general and automated computer aided design tools which enable researchers from different fields to quickly design and synthesize nucleic acid nanostructures could play a significant role. Working in the framework of the robust DNA origami approach, this dissertation presents a novel, highly general and highly automated design approach for the design and synthesis of 2D and polyhedral DNA nanostructures suitable for e.g. biomedical applications. Grounded on graph-theoretic principles, the method introduces an Eulerian tour based approach for topologically routing DNA strands into nanoscale geometries exhibiting complex features. By employing an implementation of the design method, the impact of wireframe architecture on material efficiency and stiffness of DNA nanoscale assemblies was experimentally investigated. Motivated by the design of wireframe DNA nanostructures, we develop an algorithm for finding unknotted DNA strand routings on topologically more complex higher-genus mesh wireframes. Alternatively, cotranscriptionally folding RNA nanostructures have great potential for cell-based mass production of nucleic acid nanostructures. However, the presence of the cotranscriptional complex can present obstacles to folding a target shape. In this dissertation, we propose a graph-theoretic design framework which minimizes the risk of folding traps in a cotranscriptional setting.
Supervising professor
Orponen, Pekka, Prof., Aalto University, Department of Computer Science, Finland
Thesis advisor
Orponen, Pekka, Prof., Aalto University, Department of Computer Science, Finland
DNA, RNA, nanotechnology, self-assembly, molecular folding, origami, graphs, surfaces, knots
Other note
  • [Publication 1]: Erik Benson, Abdulmelik Mohammed, Johan Gardell, Sergej Masich, Eugen Czeizler, Pekka Orponen, Björn Högberg. DNA rendering of polyhedral meshes at the nanoscale. Nature, 523(7561), 441–444, July 2015.
    Full text in Acris/Aaltodoc:
    DOI: 10.1038/nature14586 View at publisher
  • [Publication 2]: Erik Benson, Abdulmelik Mohammed, Alessandro Bosco, Ana I. Teixeira, Pekka Orponen, Björn Högberg. Computer-aided production of scaffolded DNA nanostructures from flat sheet meshes. Angewandte Chemie International Edition, 55(31), 8869–8872, July 2016.
    Full text in Acris/Aaltodoc:
    DOI: 10.1002/anie.201602446 View at publisher
  • [Publication 3]: Abdulmelik Mohammed, Mustafa Hajij. Unknotted strand routings of triangulated meshes. In Lecture Notes in Computer Science, 10467, 46–63, DNA Computing and Molecular Programming, Austin, USA, September 2017.
    DOI: 10.1007/978-3-319-66799-7_4 View at publisher
  • [Publication 4]: Erik Benson, Abdulmelik Mohammed, Daniel Rayneau-Kirkhope, Andreas Gådin, Pekka Orponen, Björn Högberg. Effects of design choices on the stiffness of wireframe DNA origami structures. ACS Nano, 12(9), 9291–9299, September 2018.
    DOI: 10.1021/acsnano.8b04148 View at publisher
  • [Publication 5]: Abdulmelik Mohammed, Pekka Orponen, Sachith Pai. Algorithmic design of cotranscriptionally folding 2D RNA origami structures. In Lecture Notes in Computer Science, 10867, 159–172, Unconventional Computation and Natural Computation, Fontainebleau, France, June 2018.
    DOI: 10.1007/978-3-319-92435-9_12 View at publisher