The interaction between protein molecules and the hydroxyapatite (HAP) crystal is an important research topic in many fields. However, the nature of their noncovalent bonding is still not clear at the atomic level. In this work, molecular dynamics simulation, steered molecular dynamics simulation, and quantum chemistry calculations were used to study the adsorption-desorption dynamics of BMP-2 on HAP (001) surface. The results suggest that there are three types of functional groups through which BMP-2 can interact with HAP crystallite, and they are −OH, −NH2, and −COO−. Based on the different orientations of protein, each might interact with HAP crystallite individually, or, two or three of them can work cooperatively. Concerning the mechanisms of interaction, it is found that the water-bridged H-bond plays an important role, which is the main force for groups without net charges. If there were more than one set of adsorption groups for a certain orientation of protein, the adsorption-desorption process would likely be stepwise. On the contrary, if there were only one set, there would be only the key-adsorption period. The results of density functional theory calculations confirm the actual existence of this type of water-bridged H-bond. Furthermore, it is also found that the CHARMM27 force field could provide correct structural information qualitatively, although the data are slightly different from those obtained by UB3LYP/6-31G* method.
