Adsorption mechanism of BMP-7 on hydroxyapatite (001) surfaces

https://doi.org/10.1016/j.bbrc.2007.06.169Get rights and content

Abstract

Many properties and functions of bone-related proteins perform through the interface with the hydroxyapatite. However, the mechanism of difference of proteins adsorbing behaviors caused by the variation of calcium and phosphate ions on hydroxyapatite is still unclear at atomic level. In this work, we investigated the site-selective adhesion and the adsorption mechanism of protein BMP-7 to the hydroxyapatite surfaces in aqueous media during adsorption and desorption processes. Molecular dynamics (MD) and steered molecular dynamics (SMD) simulations combined with trajectory analysis were employed to give insight into the underlying behaviors of BMP-7 binding. The results suggest that the adsorption sites could be divided into two categories: COO– and NH2/NH3+. For COO–, the adsorption phenomenon is driven by the electrostatic interaction formed between the negative charged carboxylate groups and the Ca1 cations on the hydroxyapatite surface. While for NH2/NH3+, the interaction is through the intermolecular H-bonds between the N-containing groups and the phosphate on the hydroxyapatite surface.

Section snippets

Simulation details

The initial structure of BMP-7 was taken from the protein data bank (PDB Accession No. 1M4U). The original module of HAP (P63/m) was extracted from the American Mineralogist Crystal Structure Database [19] and its unit-cell parameters are a = b = 0.943 nm and c = 0.688 nm.

In order to obtain the optimized geometry of BMP-7, an energy minimization was firstly performed, and a 1 ns MD relaxation in water media (with normal density, SPC model [20]) was followed. Then two simulation systems, which were

Equilibrium adsorption

The MD simulation is essential to achieve an equilibrium state, and generally the potential energy of biomolecule was used to judge whether the system achieves equilibrium or not. To describe the adsorption states, the potential energy of biomolecule was extracted individually from the simulation systems [12], [26]. It was defined as Epot = Etot − Ekin, where Epot is the potential energy, Etot is the total energy, and Ekin is the kinetic energy of the protein. Fig. 1 illustrates the potential

Conclusion

The adsorption sites and the adsorption mechanism of BMP-7 (one of the bone morphogenetic proteins, BMPs) onto the hydroxyapatite (HAP) surfaces were investigated from atomic level. It is reported that the Ca/P ratios on the HAP surface have great contribution to the adsorption of proteins onto the HAP. In this work, two extreme HAP surfaces were discussed. System I represents the surface sliced only including the Ca1 cations, while System II represents the surface sliced including Ca2 and

Acknowledgment

This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 60533050 and 20576112).

References (28)

  • L. Kalé et al.

    NAMD2: greater scalability for parallel molecular dynamics

    J. Comp. Phys.

    (1999)
  • B. Isralewitz et al.

    Steered molecular dynamics investigations of protein function

    J. Mol. Graph. Model.

    (2001)
  • W. Humphrey et al.

    VMD: visual molecular dynamics

    J. Mol. Graph.

    (1996)
  • A. Matsuda et al.

    Surface modification of a porous hydroxyapatite to promote bonded polymer coatings

    J. Mater. Sci. Mater. Med.

    (2003)

    • Cited by (0)

    View full text
    Copyright © 2007 Elsevier Inc. All rights reserved.