Computer aided design of antimicrobial surface
Creators: name: LI, Wenxuan
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 340309
subject: Theory and design of materials
classificationCode: 340799
subject: Theoretical and computational chemistry not elsewhere classified

description: This project involves the development of a novel computational method for screening for chain molecules with antifouling potential based on the atomistic solution-based simulations and the coarse-grained level modelling of the interaction between the nano-protrusions and lipid membranes in order to study the effects of surface topography on fungal cell membrane disruption. The solution-based screening method enables investigating the antifouling ability of potential chain molecules without recourse to computationally expensive simulations of protein adsorption on surface, which can provide a baseline for future in silico design experiments, while the coarse-grained models can provide the mechanisms of membrane disruption induced by the surface topography at molecular scale, which can further help the design of antibacterial nanomaterials.<br><br>

A detailed description of the motivation for this project, and a literature review on important experimental discoveries in antifouling coatings and the molecular modelling of antifouling coatings are presented in Chapter 1. Also, additional literature reviews are included in the introductory sections of Chapter 3 to 5 pertinent to the subject matter in question.<br><br>

Quantum mechanics, classical molecular mechanics and coarse-grained models are three of the most important computational techniques that are currently used in computational modelling of antifouling coatings. In this project, classical molecular mechanics (force-field) methods are employed to describe the physical interactions between proteins and selected chain molecules, and coarse-grained models are applied to describe the interactions between the nano-protrusions and the dioleoylphosphatidylcholine (DOPC) membrane. In addition, molecular dynamics is used to obtain time and temperature-dependant properties of these protein/chain molecules and membrane/protrusions systems. A detailed description of the computational techniques is included in Chapter 2. <br><br>

Hall-Stoodley et al. found the attachment of large biological substance on surfaces is mediated by the adsorbed proteins, indicating that understanding the protein adsorption is essential for elucidating the mechanism of biofouling and further employing rational design to produce more sophisticated antifouling systems. Recently, it was shown via molecular dynamics (MD) simulations that the adsorption behaviour of proteins on poly(ethylene glycol) (PEG) and poly(phosphoesther) coated nanoparticles could be predicted through examination of the amino acid composition on protein surfaces. As a potentially critical shift away from computationally challenging protein adsorption simulations, this type of bulk phase simulation may potentially open up other avenues to design/screen for ligands with antifouling potential. In Chapter 3, we presented a novel computational model to investigate the association of specific co-solvent on a protein surface by immersing the protein in a water-co-solvent solution. The alcohols were firstly used as co-solvent to study the analogous protein/water/alcohol ternary model, because alcohols are simple molecules with a variety of hydrophobicity. Analysis was developed to identify appropriate metrics to characterise the affinity of alcohol molecules for the protein surface. Then the affinity of a collection of antifouling molecules on protein surface was investigated through molecular dynamics simulations when protein was immersed in an antifouling molecules-water solution. Same analysis developed from alcohol simulations was applied to investigate the protein affinity with antifouling chain molecules in antifouling chain molecule-water simulations. This analysis allows for the determination of whether antifouling chain molecules associate more or less with the protein surface and provides a baseline for future in silico design experiments.<br><br>

To test the efficacy of the solvent based screening method, in Chapter 4, the adsorption of protein on PEG-grafted silica surface was investigated to provide comparison between the protein adsorption simulation and solution based screening method. Specifically, the association behaviour for each residue in protein surface with PEG chains was investigated and compared with results from solution based simulations. The solution based simulations were found to be able to provide useful information about identifying the key residues for the adsorption behaviour and showing the different adsorption extent of the same ligand with different proteins when compared with protein adsorption simulations. This finding has supported the idea that the simplified model and analysis tools developed from the solution based simulations have potential for computationally screening for ligands with antifouling potential without recourse to computationally expensive simulations of protein adsorption on surfaces.<br><br>

Antifouling coatings are perhaps the most common method of biofouling control, but limitations, such as toxicity, ease of oxidation and limited durability, have dictated the need for more robust antifouling materials. High-aspect-ratio nano-protrusions have been found to be able to kill bacteria on contact based solely on their physical surface structure, making them very promising as antifouling materials. Many experimental studies have been performed to study the key factors that affect the disruption of membranes. However, the feasible parameters of the nano-protrusions are restricted. In Chapter 5, a coarse-grained model was proposed to study the effect of surface topography on the disruption of DOPC membrane. Steered molecular dynamics (SMD) simulations were performed to push the DOPC bilayers to contact with the fixed nano-protrusions. By comparing the pushing force and contact area for nano-protrusions to penetrate the DOPC bilayers, the most appropriate shape, size and density of nano-protrusions to disrupt the bilayers can be acquired. This universal methodology can be further applied to investigate the effect of surface topography on disruption of different membranes, which would be very useful for the design of antibacterial nanomaterials.<br><br>

From the knowledge gained, we have developed a novel atomistic model for screening for chain molecules with antifouling potential and a coarse-grained model for helping elucidate the mechanism of membrane disruption induced by the nano-protrusions. These models are summarized in Chapter 6 and our future work is presented in the final chapter of this thesis.