Molecular Dynamics Simulation of the Early Stages of Nucleation of Hydroxyapatite at a Collagen Template

Abstract

We have used molecular dynamics simulations to investigate the early processes in the nucleation of hydroxyapatite at a collagen template, by immersing a triple-helical collagen molecule in a stoichiometric solution of Ca 2+, PO 4 3–, and OH – ions, where we have observed the formation of calcium phosphate clusters at the collagen template. Electrostatic attractions were prevalent between calcium ions and oxygen atoms of the glycine and hydroxyproline residues, which were the starting point for the formation of the calcium phosphate clusters. Some phosphate ions form hydrogen-bonds with the hydroxy groups of hydroxyproline residues, whereas most of the hydroxy ions stay in solution, although some become attached to calcium phosphate clusters. The observed nucleation and clustering is too early in the hydroxyapatite formation process to show differentiation between distinct hydroxyapatite surfaces. However, calculations of the interaction of a collagen peptide with the (0001) and (011̅0) surfaces of hydroxyapatite show a clear energetic preference by the peptide for adsorption at the (011̅0) surface, which suggests that in the presence of the collagen matrix the hydroxyapatite crystal would grow more rapidly in the (0001) direction and express the (011̅0) surface in the particle shape, in agreement with the observed morphology of biological hydroxyapatite.