Force Field Parameters and Atomistic Surface Models forHydroxyapatite and Analysis of Biomolecular Adsorption at Aqueous Interfaces

Biomineralization of human bone and teeth are highly associated with interactions between biomolecules and hydroxyapatite (HAP). Available force fields require specific mixing rules to describe HAP interactions with biomolecules and lack validation of polarity, interfacial interactions, as well as surface chemistry. We present a new force field for HAP which is fully integrated into the polymer consistent force field (PCFF), CHARMM, and AMBER. In addition, models of hydrated HAP surfaces are critical under physiological conditions and have rarely been addressed in previous simulation studies. The proposed force field parameters and surface models of HAP are validated by lattice structures from X-ray studies, IR spectrum, elastic constants, cleavage energies, and immersion energies in water from measurements. The validation shows substantial improvements in accuracy compared to previous models, including small deviations in cell parameters, elastic constants, and full consistency with known data on surface and immersion energies for monohydroxylated and dihydroxylated surfaces. We propose models for {001}, {010}, {020}, and {101} surfaces based on stoichiometric hydration reactions that are tunable according to pH. The protonated surface models were further tested to analyze interactions with a known HAP binding peptide, SVSVGGK, which showed attraction to {001}, {010}, and {020} surfaces and less attraction to {101} surfaces. The binding is mediated by interactions of ammonium groups on the K side chain and at the N terminus with superficial monohydrogen phosphate groups in agreement with NMR studies, as well as by coordination of superficial calcium ions by the C terminus. Furthermore, three bisphosphonate molecules used for osteoporosis, pamidronate, ibandronate, and zoledronate, were also tested on protonated {001}, {010}, {020}, and {101} surfaces corresponding to pH 5. The P-C-P motif of bisphosphonates interacts with the protonated phosphate by hydrogen bonding or coordinates with the remaining calcium on the surface. The charged nitrogen group in the pamidronate and ibandronate did not show preference the surface due to their hydrophilic side chains, but the imidazolium ring in zoledronate was pushed toward to the surface due to its hydrophobic character. The observation from the zoledronate could correlate its longer retention time found in experimental studies and HAP chromatography.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Polymer Engineering

Grantor dc:publisher

University of Akron

Year dc:date

2013

Author dc:creator

• Lin, Tzu-Jen

Contributors dc:contributor

• Heinz, Hendrik

• Physical Chemistry
• Hydroxyapatite
• Molecular Dynamics
• Surface Models

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=akron1365511604

OAI identifier oai:identifier

oai:etd.ohiolink.edu:akron1365511604