Over the past two decades the development of self-assembling peptide molecules has flourished. By focusing on short inexpensive sequences chemists have been able to distil the key contributors to and modalities of specific chemical functionality in self assembly. The synergy of laboratory and in silico experimentation has been key to this progress, where simulations can both direct discovery and rationalise experimental observations.
To refine material design, research interest has turned to peptide isomers and mimics, of which peptoids are an intriguing class. Peptoids possess many appealing characteristics including biomedically relevant properties, sequence dependant assembly etc. A review of current peptoid assembly research is provided. To enable computer informed discovery, a major part of this thesis has been to develop atomistic and coarse-grained (CG) peptoid forcefields.
Simulations of short assembling peptoids with these models have provided insights into sidechain - backbone dynamics and assembly growth processes. Aliphatic chemistry, making up a fifth of the natural amino acids, is less commonly found in assembling sequence design, in favour of aromatic groups.
In recognition of this imbalance a focus of this thesis has been to examine assemblies which employ such functionality, and this thesis work has discovered a novel mode of crystallization at interfaces, exhibited by both aliphatic peptoid bases and amino acids. This phenomenon was rationalised and found to be quite general. The effect of sidechain bulk was also investigated by comparing the assemblies of all fluorenylmethoxycarbonyl (Fmoc) conjugated aliphatic amino acids in mixed solvent conditions.
This thesis culminates with the study of a chemically fuelled assembly of FmocAVD which undergoes a morphological transition within a reaction cycle. To examine this observation a reactive forcefield was used: it was found that feedback between termini repulsion and backbone reordering was shown to be the driver of this process. The findings described within this thesis will be informative for the future design of novel assembling peptoid and peptide materials.
| Date of Award | 24 Jul 2024 |
|---|
| Original language | English |
|---|
| Awarding Institution | - University Of Strathclyde
|
|---|
| Supervisor | Tell Tuttle (Supervisor) & K H Aaron Lau (Supervisor) |
|---|