Molecular modeling of inhibition of hydroxyapatite by phosphocitrate

A. Wierzbicki, Herman S Cheung

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Hydroxyapatite is one of the most important minerals in the human body. It constitutes almost the entire mineral phase of bones and tooth enamel. Its ubiquity, however, sometimes may lead to cases of unwanted biomineralization that results in many pathological conditions. Recently, it has been shown in vitro that the growth of hydroxyapatite crystals can be efficiently controlled using phosphocitrate, a naturally occurring compound. Phosphocitrate has been shown also to prevent sticking of cells to hydroxyapatite crystals. However, the molecular mechanism of phosphocitrate interactions with hydroxyapatite crystals was almost entirely unknown due to difficulties in analyzing the X-ray geometry of the unit cell of hydroxyapatite, which exhibits disorder in the hydroxyl ion positions. This study presents the first, to our knowledge, molecular modeling investigations of inhibition of hydroxyapatite crystals. We have used the Generalized Gradient Approximation of Density Functional Theory with the implementation of full periodic boundary conditions to optimize the positions of hydroxyl ions in the unit cell of hydroxyapatite crystal. We have applied molecular modeling to show that phosphocitrate binds to (100) crystal faces of hydroxyapatite, and we have analyzed the nature of stereospecificity of recognition and binding to these planes. We propose that the binding of phosphocitrate to the (100) face of hydroxyapatite induces morphological changes that may lead to diminished crystal growth or to its total cessation, and may also prevent cell sticking to hydroxyapatite. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)73-82
Number of pages10
JournalJournal of Molecular Structure: THEOCHEM
Volume529
DOIs
StatePublished - Sep 8 2000

Fingerprint

Molecular modeling
Durapatite
Hydroxyapatite
crystals
Crystals
cells
minerals
Crystallization
enamels
human body
Minerals
teeth
bones
Tooth enamel
phosphocitrate
crystal growth
ions
Biomineralization
disorders
boundary conditions

Keywords

  • Crystal morphology
  • Hydroxyapatite
  • Inhibition
  • Molecular modeling
  • Phosphocitrate

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics
  • Atomic and Molecular Physics, and Optics

Cite this

Molecular modeling of inhibition of hydroxyapatite by phosphocitrate. / Wierzbicki, A.; Cheung, Herman S.

In: Journal of Molecular Structure: THEOCHEM, Vol. 529, 08.09.2000, p. 73-82.

Research output: Contribution to journalArticle

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