Unveiling the mechanism of an amelogenin-derived peptide in promoting enamel biomimetic remineralization

Amelogenin and its derived peptides have exhibited excellent efficacy in promoting enamel biomimetic remineralization. However, little is known about their specific action mechanisms. Herein, by combining experiments and computer simulation, the mechanism of an amelogenin-derived peptide QP5 in regulating enamel biomimetic remineralization is unveiled for the first time. In experiments, peptide QP5 was separated into (QPX)5 and C-tail domains, the interactions of peptide-minerals in nucleation solution and the regulation of peptide on enamel biomimetic remineralization were explored. QP5 exhibited an unordered conformation when mineral ions existed, and it could adsorb on minerals through its two domains, thereby inhibiting spontaneous nucleation. The remineralized enamel regulated by C-tail showed better mechanical properties and formed more biomimetic crystals than that of (QPX)5, indicating the C-tail domain of QP5 played an important role in forming enamel-like crystals. The simulation results showed that the conformation of QP5 changed greatly, mainly exhibiting 13-bend, 13-turn, and coil structures, and it eventually adsorbed on enamel through negatively charged residues of the C-tail domain, then captured Ca2+ from solution to promote enamel remineralization. This study improved the evaluation methods of the mechanism of biomimetic peptides, and laid a theoretical basis for the amelioration and clinical transformation of peptide QP5.

Automated summary

The mechanism of amelogenin-derived peptide QP5 in regulating enamel biomimetic remineralization is uncovered for the first time using a combination of experiments and computer simulation. QP5 inhibits spontaneous nucleation by adsorbing onto minerals through its two domains. The C-tail domain plays a significant role in the formation of enamel-like crystals. QP5 adsorbs onto enamel and captures Ca2+ from solution to promote enamel remineralization.