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The aim of this thesis is to understand the interactions of peptides with surfaces so that we can potentially exploit this information in the control of adsorption of biomolecules on surfaces. The study concentrates on titania surfaces which have specific applications, e.g. in biosensors and titania implants. A peptide, RKLPDA, which was experimentally found to be strong-binding to titania is studied by molecular dynamics [1]. The interaction of the rutile (110) surface with water is considered and molecular dynamics simulations are performed using the Bandura/Predota model for titania [2, 3] and TIP3P water [4, 5]. It is found that there is significant water structuring both perpendicular to the surface and in the orientation of the water molecules due to the surface. It is shown that the results agree with X-ray truncation rod experiments [6] and other simulations that use SPC/E water. MD simulations of the RKLPDA peptide in water are made using the Charmm27/TIP3P force-field. It is found that the water structuring at the charged groups, Asp, Arg and Lys is significant and likely to influence its behaviour, especially when close to the structured water at titania. Experimental decreases in binding affinity of the peptide on titania upon mutation of the Pro for Ala have been suggested in terms of an increase in the flexibility of the backbone. The work described in this thesis suggests that the Lys-backbone carbonyl and Lys/Asp interactions are responsible for experimentally observed increases of the Lys-mutant compared to the unmutated peptide. MD simulations of the RKLPDA peptide adsorbed onto the titania surface with explicit water molecules are performed. It is shown that the charged groups bind to the structured water layers, not the surface itself, in a 'horseshoe' structure first proposed by Sano and Shiba [1]. Examples are shown where the Lys-mutant stays bound to the surface but the unmutated peptide does not, and where the unmutated peptide binds to the surface but the Pro-mutant does not. These follow the trends shown by experiment and indicates a conformational aspect to binding. |
