Molecular modelling of a multiphosphorylated sequence motif bound to hydroxyapatite surfaces

Proteins and peptides containing the multiphosphorylated motif -Ser(P)-Ser( P)-Ser(P)- -Glu-Glu- stabilise amorphous calcium phosphate (ACP) in body fl uids and bind with high affinity to crystalline calcium phosphate phases su ch as hydroxyapatite (HA) regulating crystal growth. Binding of this motif to hydroxyapatite surfaces was investigated in this study using molecular m odelling techniques. Using a three-step computational procedure, we have de termined the relative binding energies of the motif Ser(P)-Ser(P)-Ser(P)-Gl u-Glu to different crystalline surfaces of HA. This analysis revealed prefe rences of the motif for (100) and (010) surfaces of the crystal and prefere nces for particular orientations on a given surface. These preferences are principally governed by electrostatic interactions between the crystal latt ice and the peptide with the most stable conformers adopting structures whe re alternate residues exhibit backbone angles characteristic of a beta-stra nd and values of an alpha-helix or a distorted alpha-helix, allowing maxima l interaction between the acidic side groups and surface calciums. The resu lts of this study are consistent with experimentally-derived data on the in teraction of multiphosphorylated proteins/peptides with HA and have implica tions for the role of these proteins/peptides in calcium phosphate stabilis ation and biomineralisation processes.