In silico explorations of gold–biomolecule interactions for the engineering of biomedical gold nanomaterials
Creators: name: Charchar, Patrick
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 340309
subject: Theory and design of materials
classificationCode: 340402
subject: Biomolecular modelling and design
classificationCode: 340799
subject: Theoretical and computational chemistry not elsewhere classified

description: This thesis employs computational molecular modelling techniques to explore the physicochemical interactions occurring at the interface between gold nanomaterials and their biological coatings in order to better understand, predict, and ultimately design the properties of novel biomedical devices. In direct collaboration with experimental research, atomistic classical molecular dynamics (MD) simulations are used to investigate ligand conformational behaviour, reveal structure–property relationships, and guide the effective engineering of three distinct functionalised gold nanomaterial systems. A general introduction is given in Chapter 1 to provide a background into the appeal of gold nanomaterials for biological applications, including an outline of the unique size-dependent properties these fascinating materials possess and examples of how nanogold-based devices are revolutionising diagnostic methods and the treatment of disease. In the subsequent Chapter 2, the current successes and challenges associated with multiscale computational strategies for simulating Au–bio systems, from electronic structure calculations to force field methods, are given to illustrate links between different approaches and their relationship to experiment and applications. In Chapter 3, a methodological overview of physics-based computational techniques is presented, focusing on gold interfacial all-atom classical MD due to its application in this thesis. Chapter 4 utilises MD to clarify the conformations adopted by different peptide-monolayers on Au(111) surfaces and explores how these relate to the experimental efficacy of an in vitro diagnostic approach, which identifies and quantifies the presence of disease marking antibody molecules in solution. The peptide-monolayers formed on Au(111) are found to be intimately related to the inclusion and location of particular amino acids in individual peptide chains of the monolayers, with certain residues strongly influencing the conformational landscapes exhibited. The complex gold–peptide topographies and solvent exposure of antibody-specific residues correlate well with empirical performance and provide non-intuitive characterisations of the assemblies unattainable through experiments. To study how peptide-ligand conformations affect the photoluminescence (PL) properties of Au25 nanoclusters that are capable of in vivo bioimaging, MD is used in conjunction with quantum mechanical calculations in Chapter 5. Following the systematic MD modelling of different Au25(SP)18 nanoclusters (where P = hexapeptide), properties such as peptide arrangement, hydrodynamic radii, distribution of chemical groups around the gold core, water structuring, and hydrogen bond networking are each correlated with experimentally measured AuNC PL. Key findings from this chapter present design principles to optimise the PL of these systems and postulate potential mechanisms for PL quenching. Next, Chapter 6 employs MD to examine octanethiol-protected Au25 nanoclusters, which are inherently hydrophobic and form an integral component in a composite gold–silica theranostic material. Simulations in explicit water and ethanol solvents reveal significant structural differences in the alkanethiol ligand layers on Au25(SC8H17)18 and these differences are then used to hypothesise a steric–kinetic mechanism to explain performance issues that these materials face in their drug delivery applications. The outcomes of this thesis contribute to the overall understanding of organic–inorganic materials in targeted applications through exploring the intricate interactions that occur on the nanoscale. This work also highlights how the synergistic union of theoretical and experimental approaches can be used to produce translational research, improve insight, and facilitate the development of biocompatible gold nanomaterials for applications in the fields of bioimaging, biosensing, drug delivery, and biomedicine in general.<br>