Effect of Hydroxyapatite Surface on BMP-2 Biological Properties by Docking and Molecular Simulation Approaches

The interactions between osteogenic proteins and the biomaterial surface are crucial to the application of biomaterials, in which the conformational or orientational change of the adsorbed protein on the solid surfaces is one of the most important interactions other than the protein adsorption. Although some progress has been made in the mechanism of protein adsorption on the surface of hydroxyapatite (HAP) in recent years, there is still insufficient atomistic/molecular information about the conformation and orientation of proteins upon adsorbing on solid surfaces. In this study, different orientations and conformations of bone morphological protein-2 (BMP-2) adsorbed on the surface of HAP were calculated through the protein–solid surface docking approach; the relationship between optimal adsorption and biological activity of BMP-2 was investigated by applying a combination of molecular dynamic simulation (MD) and steered molecular dynamic simulation (SMD). Two optimal adsorption conformers were screened out according to the docking results on the basis of orientations of BMP-2 with different epitopes. Subsequent MD and SMD results showed that the knuckle epitope of BMP-2 was easier to adsorb on the surface of HAP(100) than the wrist epitope accompanying certain conformational changes. Such an absorption mode led to the wrist epitope of BMP-2 being exposed to the environment and then being identified/interacted with type I receptors on the stem cell membrane, which further induces the differentiation of stem cells into osteoblasts. Current simulation provided a theoretical high-throughput screening method for the protein–biomaterial adsorption states. It can be extended to more research on different protein adsorptions on the surface of different materials. The simulation results provided more information at the molecular and atomic levels to further interpret the mechanism of osteoinductivity from the perspective of growth factor adsorption. Meanwhile, we believe that it should be a meaningful attempt to screen biomaterial key factors by the high-throughput method, which might become a promising way to develop or optimize new biomaterials.