Electronic Thesis and Dissertation Repository


Doctor of Philosophy


Applied Mathematics


Dr. Mikko Karttunen, Dr. Graeme K. Hunter


We present molecular dynamics (MD) simulations providing information about the mechanisms of biomineralization. We focus on osteopontin-related peptides, which inhibit the growth of calcium oxalate monohydrate (COM) the primary constituent of kidney stones.

First, we performed two ab initio MD simulations: aspartic acid (Asp) and the dimer of aspartic acid and phosphoserine (Asp-pSer) interacting with a fully hydrated COM crystal slab exposing the {100} face. For Asp we found that one of the carboxyl and the amine group both interact with the crystal surface but neither forms a stable contact during the simulation. Asp-pSer interacts preferably with its carboxyl groups with the calcium ions of COM. Once a contact is formed, it remains stable for the remainder of the simulation. Comparing the results of Asp and Asp-pSer shows that even though during our simulation the phosphate group did not directly interact with the COM surface its presence results in a stronger interaction of the carboxyl groups with the crystal slab. This fact and the agreement in the bond length between the carboxyl oxygen of the amino acids and the calcium ions of COM in these ab initio and previously performed classical MD simulations validate the model used in the classical MD simulations.

Second, we performed classical MD simulations of the growth-inhibiting, acidic peptides pOPAR and poly-glu interacting with the {100} and {010} faces of COM containing {121} growth steps. For both peptides similar results were found. In the system with the {100} terraces and the {121} steps the peptides interact with the terrace ({100} face). In the system with the {010} terraces and the {121} steps on the other hand the peptides interact with the step ({121} face). The negatively charged peptides make their choice of adsorption based on the densities of calcium ions on the surface of the different COM faces, the order of adsorption strength is the same as the density of calcium ions: {100} > {121} > {010}. These results are in agreement with experiments measuring the inhibiting effect of the peptides on COM crystals grown in the peptide’s presence.