Forster, Joel Calum;
(2022)
In Silico Evolution of Biomolecular Assemblies.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The relationship between form and function of biomolecular machinery often proves challenging to isolate. Attempts to gain intuition of the underlying physics must first identify the key structural features and relate them by some model to behaviour. In this dissertation we take a reverse engineering approach. We outline a methodology using evolutionary algorithms, coupled with coarse grained models and molecular dynamics simulations, to identify and extract novel physics in systems under study. By allowing an algorithm to explore and iterate upon structure we were able to uncover new, non-trivial, design principles which did not follow purely from observation. We begin with the consideration of passive cargo uptake by a cell membrane, allowing a patchy nanoparticle to alter the position of ligands on its surface to improve efficiency and reliability of vesicle formation. We were able to identify novel "chain-like" ligand patterns which lower the free energy barrier for membrane wrapping when compared to uniformly spaced ligands. As a next step, the methodology was applied to design self-assembling fibrillar networks of collagen-mimetic molecules. Computational methods were developed which allowed the characterisation of network properties. This routine was applied to probe the global properties of collagen-mimetic molecules across a range of binding energy strengths. We show that measurements of graph topology reflect system structure. Finally, we evolve collagen-mimetic molecules to target a specific periodic patterning (d-period). The resulting simulations are then characterised, establishing a region where d-period can be predicted and controlled for such a system. It is hoped that the methodology and the novel results presented here offer new insights into the future of rational design of self-assembly at the nanoscale.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | In Silico Evolution of Biomolecular Assemblies |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy UCL > Provost and Vice Provost Offices > UCL BEAMS UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10158293 |
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