Simulation Insight into the Synergic Role of Citrate and Polyaspartic Peptide in Biomineralization

Hydroxyapatite (HAP) is one of the most important inorganic components in biological minerals such as bones and teeth. More than 90% of the total citrate is accumulated in human bones and other biomineralized tissues. In addition, mineralizing proteins are enriched in glutamate and aspartate residues, which are important for their mineral-regulating properties. However, how citrate ions (CITs) and/or acidic amino acids regulate the formation of HAP is still unclear. In this work, molecular dynamics simulations were performed to study how CIT regulates the adsorption behavior of polyaspartic acid (PASP) on the HAP surface in the calcium phosphate solution. The simulation results indicate that PASP can be used as an ion chelator to complex Ca²⁺ and can serve as templates for HAP mineralization by templating the distribution of Ca²⁺ on its surface, which are attributed to the -COO^- and α-helix structure. Most importantly, the orientation distributions of PASP in all systems are narrower with the help of CIT, thereby PASP can be adsorbed on the HAP surface stably with a "lying-down" orientation. This indicates that CIT can be used as a bridging agent to bond the acidic peptide to the HAP surface in biomineralization. Thus, the synergic role of CIT and the acidic peptide on the HAP surface were revealed in this work, which can provide new insights into the interfacial phenomena during the biomineralization.