ORA Thesis: "Coarse-grained modelling of DNA and DNA self-assembly" - uuid:b2415bb2-7975-4f59-b5e2-8c022b4a3719




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Reference: Thomas Ouldridge, (2011). Coarse-grained modelling of DNA and DNA self-assembly. DPhil. University of Oxford.

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Title: Coarse-grained modelling of DNA and DNA self-assembly


In this thesis I present a novel coarse-grained model of deoxyribonucleic acid (DNA). The model represents single-stranded DNA as a chain of rigid nucleotides, and includes potentials to represent chain connectivity, excluded volume, hydrogen-bonding and base stacking interactions. The parameterization of these interactions is justified by comparing the model's representation of a range of physical phenomena to experimental data. In particular, the geometrical structure and elastic moduli of duplex DNA, and the flexibility of single-stranded DNA, are shown to be physically reasonable. Additionally, the thermodynamics of single-stranded stacking, duplex hybridization, hairpin formation and more complex motifs are shown to agree well with experimental data.

The model is optimized for capturing the thermodynamic and mechanical changes associated with duplex formation from single strands. Considerable attention is therefore given to ensuring that single-stranded DNA behaves physically, an approach which differs from previous attempts to model DNA. As a result, the model is the first in which an explicit stacking transition is present in single strands, and also the only coarse-grained model to date to capture both hairpin formation within a single strand and duplex formation between strands.

The scope of the model is demonstrated by simulating DNA tweezers, an iconic nanodevice -- the first time that coarse-grained modelling has been applied to dynamic DNA nanotechnology. The simulations suggest that branch migration during toehold-mediated strand displacement -- a central feature of many nanomachines -- does not have a flat free-energy profile, as is generally assumed. This finding may help to explain the observed dependence of displacement rate on toehold length.

Finally, the operation of a two-footed DNA walker on a single-stranded DNA track is considered. The model suggests that several aspects of the walker will reduce its efficiency, including a tendency to bind to an undesired site on the track. Several design modifications are suggested to improve the operation of the walker.

Digital Origin:Born digital
Type of Award:DPhil
Level of Award:Doctoral
Awarding Institution: University of Oxford
Notes:An errata has been added to this thesis.
About The Authors
institutionUniversity of Oxford
facultyMathematical,Physical & Life Sciences Division - Physics - Theoretical Physics
researchGroupOxford Theory of Soft Matter
oxfordCollegeKeble College
fundingEngineering and Physical Sciences Research Council
Dr Adriaan A. Louis More by this contributor
Bibliographic Details
Issue Date: 2011
Copyright Date: 2012
Urn: uuid:b2415bb2-7975-4f59-b5e2-8c022b4a3719
Item Description
Type: thesis;
Language: en
Member of collection : ora:thesis
Alternate metadata formats
Copyright Holder: Thomas Ouldridge
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