@phdthesis{Friedrichs2014,
  author    = {Wenke Friedrichs},
  title     = {Simulations of Short Model Peptides and Practically Relevant Modeled Titanium Implant Surfaces},
  journal    = {Simulation kurzer Modellpeptidsequenzen sowie praxisnaher ver{\"a}nderter titanbasierender Implantatoberfl{\"a}chen},
  url       = {https://nbn-resolving.org/urn:nbn:de:gbv:9-002099-1},
  year      = {2014},
  abstract  = {One of the aims of this work was to generate a non restrained force field model including carbon contamination to make the adsorption simulations more realistic and comparable with experimental data. Another purpose was to find out how the special recognition of small linker proteins on titanium dioxide is working. During this work a fixed and a non restrained rutile (100) model was used and critical properties were observed which are not only related to the surface. The rigid water layers on top of the oxide are very important for the protein and peptide adsorption. Therefore the first discussing object were the properties of the water layers and how they can be influenced. The charge distribution on the surface was found to have a big effect on them. Depending on the charges of the surface atoms or the functional groups, resulting out of the hydroxylation equilibrium, precisely the first water layer gets more rigid or smother. This has a big effect on biomolecule adsorption. The peptides need to penetrate these water layers to generate direct interaction points. The correct description of the surface in molecular dynamic simulations therefore has a high influence on the results. The better the model is the better the findings are comparable with experimental ones. Additionally carbon contamination was mimicked by using a monolayer of pentanol molecules. This fits very good with experimental data (e.g. contact angle) and make the oxide model more hydrophobic. Interaction of proteins and peptides in experiments or in medical use are often observed under normal air conditions, which means that the scaffold is i) hydroxylated by water and ii) carbon contaminated in a short period of time. Therefore investigations were done to find out how the contamination influences the adsorption of a formally know good or bad binding peptide (TiOBP1; TiOBP2). It was found that the TiOBP1 is able to bind the different surface modifications very well which coincides with observations made in experiments. The way of adsorption (direct or indirect) depends on the water layers properties. The first layer on high charged surface models is that rigid, that the peptide is not able to adsorb in a direct way. On the carbon contaminated oxide model the adsorption is possible by reducing the flexibility of the secondary structure motive. In the case of TiOBP2 adsorption on the clean surface model results in only weak binding or even in no interaction. Whereas on the carbon contaminated dioxide the once know bad binder is able to interact with the Pentanol monolayer. No direct adsorption is observed but the hydrophobic side chains have the possibility to orient themselves according to the hydrophobic layer without changing significantly in the secondary structure motive. An additional test peptide (minTBP) adsorbs without being affected by the contamination. This raises the question if the distribution of hydrophobic to hydrophilic amino acids has influence on the adsorption ability according to clean and contaminated surface. For experimental application it could be of interest to generated peptides (GEPI´s) which bind both surface types without changing the secondary structure motives then as we know functionality is based on these structures. In the case of the PHMB polymer adsorption was observed depending on the hydroxylation ratio and therefore on the charge density of the rutile (100) surface. After analysis of the simulations takeaways from experiments could be substantiated. The PHMB interacts with the negative charged surface via the first water layer as a film. So the new force field model describing the rutile (100) titanium dioxide surface with additional carbon contamination model of one monolayer pentanol fits the experimental data very well. The adsorption studied on this surfaces indicates that the contamination as expected makes the surface more hydrophobic and influences the adsorption behavior of the tested peptides especially the secondary structure of TiOBP1. This indeed enhances experimental investigations. Peptides which e.g. link organic and inorganic parts should be good adsorbing on clean and contaminated surfaces by keeping their functionality. Furthermore experimental data can be substantiated by using atomistic simulations like in the case of PHMB adsorption.},
  language  = {en}
}