Replica-exchange molecular dynamics simulation of basic fibroblast growth factor adsorption on hydroxyapatite

Area of Science:

• Biophysics
• Materials Science
• Biochemistry

Background:

• Basic fibroblast growth factor (bFGF) plays crucial roles in cell growth and tissue repair.
• Hydroxyapatite (HAP) is a key component of bone and tooth enamel, making it relevant for biomaterial applications.
• Understanding protein-surface interactions is vital for designing effective biomaterials and drug delivery systems.

Purpose of the Study:

• To investigate the adsorption behavior of bFGF on the hydroxyapatite (001) surface.
• To determine the preferred adsorption orientations and energies of bFGF on HAP.
• To elucidate the molecular mechanisms underlying bFGF-HAP interactions and their implications for biological signaling.

Main Methods:

• Replica-exchange molecular dynamics (REMD) simulations.
• Conventional molecular dynamics (CMD) simulations.
• Analysis of adsorption states, energies, populations, and conformational changes.

Main Results:

• REMD simulations enabled bFGF to overcome the surface water barrier and explore different adsorption states (weak, medium, strong).
• Three energetically preferred configurations were identified: heparin-binding-up (HP-up), HP-middle, and HP-down.
• The HP-middle orientation exhibited the strongest adsorption energy (-1149 ± 40 kJ·mol⁻¹) and highest population (52.1-52.6%), with significant conformational flexibility.
• bFGF adsorption orientations support both FGF/FGFR and DGR-integrin signaling pathways.
• Strong adsorption involves interactions of basic residues with the HAP surface, stabilized by geometric matching.

Conclusions:

• The HP-middle orientation is the most stable and abundant adsorption state of bFGF on HAP (001).
• bFGF adsorption on HAP can facilitate multiple biological signaling pathways, including FGF/FGFR and DGR-integrin signaling.
• The study provides insights into the molecular basis of protein-surface interactions, crucial for biomaterial design and biomedical applications.