Understanding the immobilisation of proteins on surfaces using molecular dynamics computer simulations

The study of protein adsorption on surfaces is becoming an increasingly important topic for research since it plays a crucial role in a variety of biomedical and biotechnological applications, biomaterials and cell biology research. Specific properties of surface-based diagnostic assays and cell culture supports are often determined by the site-selective attachment of proteins to solid supports. In this thesis, we investigate two different methods of immobilising proteins: the immobilisation of the Hydrophobin protein via its “hydrophobic patch” and large-scale but weak van der Waals interactions; and the immobilisation of the TagRFP protein using hexahistidine tags and fewer but stronger electrostatic interactions. Our simulations show that the Hydrophobin protein prefers to use its hydrophobic patch to adsorb to hydrophobic surfaces while it adsorbs to hydrophilic surfaces with its opposite side. On the other hand, our simulations confirm that increasing the number of hexahistidine tags attached to the tagRFP protein steadily increases the binding strength of the protein to the surface. Our results provide insight into the mechanisms driving the orientation of the protein when adsorbed. These results can help guide future simulations and experiments that wish to improve the immobilisation of proteins.