Computer Simulation Of Citrate Mediated Biomineralization On Hydroxyapatite Surfaces

As the most important mineral component in human bones and teeth,hydroxyapatite(HAP)has good biocompatibility and mechanical properties.It is an excellent material for bone or tooth restoration,so how to regulate the crystal growth of HAP is of great interest.In addition,citrate ion(CIT)in the human body is enriched at bones and teeth,which plays an important auxiliary function in biomineralization.In this work,molecular dynamics(MD)simulations were used to study the adsorption behavior of various biomineralization-related peptides on the HAP surface.The main findings are as follows.1.How CIT regulates the adsorption behavior of polyaspartic acid(PASP)on the HAP surface in calcium phosphate solution was investigated by MD simulations.The results showed that due to the carboxyl group and?-helical structure,PASP can act as ion chelator to bind Ca²⁺and form a template for HAP mineralization.After the addition of CIT,the orientation distribution of PASP in all systems was narrower and adsorbed onto the HAP surface with a"lying-down"orientation.It indicates that CIT can act as a bridging agent to mediate and stabilize the adsorption of acidic peptides on HAP surfaces.2.The mechanical behavior of osteocalcin(OCN)in the HAP layer was investigated using MD and steered molecular dynamics simulations.The reduction of the HAP gap resulted in the formation and disruption of interfacial bonds of OCN on the HAP surface and led to stick-slip motions.The addition of CIT also significantly increased the traction force due to the spatial blocking effect of the calcium citrate cluster and the binding of its calcium ions to the acid residues of OCN.All above results led to higher energy dissipation when pulling the OCN in the HAP layer.3.The adsorption behavior of osteopontin(OPN)on the HAP surface was investigated by combining MD simulations,parallel tempering and metadymics algorithms.The results showed that the combined algorithm can greatly increase the sampling efficiency.Among them,OPNA would keep a more compact structure in aqueous solution because its net charge was 0 and could not be effectively adsorbed on the HAP surface.While OPNB-OPNG had more net negative charge,they could adsorb on the HAP surface more stably.Meanwhile,as the number of phosphorylated serine(Sep)residues in OPNB-OPNG increased from 0 to 5,the radius of gyration and conformational changes also increased gradually.In addition,modification of Sep in the flexible part of the protein or peptide could maintain its?-helix structure;while increasing the number of Sep could significantly increase the radius of gyration and conformational change of the current fragment.The above discussion reveals the regulation mechanism of HAP mineralization by citrate and organic substrates in biomineralization at the molecular level,which can provide theoretical guidance for the development of biomimetic mineralization of materials and related medical research.