Replica-Exchange Molecular Dynamics Simulation of Basic Fibroblast Growth Factor Adsorption on Hydroxyapatite

The adsorption of basic fibroblast growth factor (bFGF) on the hydroxyapatite (001) surface was investigated by a combination of replica-exchange molecular dynamics (REMD) and conventional molecular dynamics (CMD) methods. In CMD, the protein cannot readily cross the surface water layer, whereas in REMD, the protein can cross the adsorption barrier from the surface water layer and go through weak, medium, then strong adsorption states with three energetically preferred configurations: heparin-binding-up (HP-up), heparin-binding-middle (HP-middle), and heparin-binding-down (HP-down). The HP-middle orientation, with the strongest adsorption energy (-1149 +/- 40 kJ.mol(-1)), has the largest adsorption population (52.1-52.6%) and exhibits the largest conformational charge (RMSD of 0.26 +/- 0.01 nm) among the three orientations. The HP-down and HP-up orientations, with smaller adsorption energies of -1022 +/- 55 and -894 +/- 70 kJ.mol(-1), respectively, have smaller adsorption populations of 27.4-27.7% and 19.7-20.5% and present smaller RMSD values of 0.21 +/- 0.01 and 0.19 +/- 0.01 nm, respectively. The convergent distribution indicates that nearly half of the population (in the HP-middle orientation) will support both FGF/FGFR and DGR-integrin signaling and another half (in the HP-up and HP-down orientations) will support DGR-integrin signaling. The major population (similar to 80%) has the protein dipole directed outward. In the strong adsorption state, there are usually 2 to 3 basic residues that form the anchoring interactions of 210-332 kJ.mol(-1) per residue or that are accompanied by an acidic residue with an adsorption energy of similar to 207 kJ.mol(-1). Together, the major bound residues form a triangle or a quadrilateral on the surface and stabilize the adsorption geometrically, which indicates topologic matching between the protein and HAP surfaces.