Dentin phosphoprotein sequence motifs and molecular modeling: conformational adaptations to mineral crystals

Molecular modeling has been used to investigate structural features of oligopeptides derived from possible primary structure motifs in highly phosphorylated dentin phosphoprotein (PP‐H), the predominant non‐collagenous protein in dentin. It contains a large number of aspartate (Asp) and phosphoserine (Pse) residues, the latter proposedly crucial for the PP‐H function as a mineral nucleator. In this work, computer fitting and subsequent structural adaptation of model peptides, built exclusively from Asp and Pse, to the known crystal structures of hydroxyapatite (HAP) and octacalcium phosphate (OCP) were performed. The results show that, when considering conformational energies of fitted single strand oligopeptides, either crystal will serve. Within a narrow range, fitting to OCP was slightly favored, except for oligo(Pse‐Pse‐Asp‐Asp), which showed a slightly better fit to HAP. Energy differences between crystal‐adapted and non‐adapted freely minimized peptides showed that oligo(Pse‐Asp) docked to either HAP or OCP were the energetically most favored adaptations. Fitting of minimized triple anti‐parallel β‐strands of oligo(Pse‐Asp) or oligo(Pse‐Pse‐Asp), motifs found in published sequences of rat, mouse, and bovine PP‐H. revealed that a (001) crystal face of HAP, but most likely not OCP, may be formed by these β‐sheet models. The former motif is more advantageous in this respect.