This thesis presents the results of computer simulation studies of the interaction of
the predominant molecules in the collagen protein with the hydroxyapatite
mineral. Using a combination of computational techniques, quantum-mechanical
methods based on the density functional theory (DFT) and molecular dynamics
simulations based on interatomic potentials, we have investigated the interface
between the collagen protein and the apatite mineral.
First we have employed electronic structure techniques (DFT) to study a range of
different binding modes of the amino acids glycine, proline and hydroxyproline,
which are major constituents of the collagen I protein, at two important
hydroxyapatite surfaces, (0001) and (0110) . We have performed full geometry
optimizations of the hydroxyapatite surface with adsorbed amino acid molecules
to obtain the optimum substrate/adsorbate structures and interaction energies. We
have also used DFT to investigate the binding of a series of representative
peptides containing hydrophobic side groups (proline), uncharged polar side
groups (glycine and hydroxyproline), and charged polar side groups (lysine and
hydroxylysine) to the hydroxyapatite (0001) and (0110) surfaces. This selection
of adsorbates has given us the opportunity to study separately the interactions of
the carboxylic acid and amine functional groups, as well as the effect of
hydroxylation and the charges of the side group, on the strength of interaction
with the surfaces.
We have also investigated the same systems in an aqueous environment using
classical molecular dynamics simulation, where we have calculated the energies and geometries of adsorption of the peptide at the surfaces of hydroxyapatite in
competition with pre-adsorbed water. Finally, we have studied the onset of
nucleation of the hydroxyapatite mineral at an entire collagen molecule in aqueous
solution
