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 CaI 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. (c) 2007 Elsevier Inc. All rights reserved.