Accurate Force Field Parameters and pH Resolved Surface Models for Hydroxyapatite to Understand Structure, Mechanics, Hydration, and Biological Interfaces

Mineralization of bone and teeth involves interactions between biomolecules and hydroxyapatite. Associated complex interfaces and processes remain difficult to analyze at the 1 to 100 nm scale using current laboratory techniques, and prior apatite models for atomistic simulations have been limited in the representation of chemical bonding, surface chemistry, and interfacial interactions. In this contribution, an accurate force field along with pH-resolved surface models for hydroxyapatite is introduced to represent chemical bonding, structural, surface, interfacial, and mechanical properties in quantitative agreement with experiment. The accuracy is orders of magnitude higher in comparison to earlier models and facilitates quantitative monitoring of inorganic-biological assembly. The force field is integrated into the AMBER, CHARMM, CFF, CVFF, DREIDING, GROMACS, INTERFACE, OPLS-AA, and PCFF force fields to enable realistic simulations of apatite-biological systems of any composition and ionic strength. Specific properties that are reproduced well in comparison to experiment include lattice constants (<0.5% deviation), IR spectrum, cleavage energies, immersion energies in water (<5% deviation), and elastic constants (<10% deviation). Interactions between mineral, water, and organic compounds are represented by standard combination rules without additional adjustable parameters and shown to achieve quantitative precision. Surface models for common (001), (010), (020), and (101) facets and nanocrystals are introduced as a function of pH on the basis of extensive experimental data. New insights into surface and immersion energies, the structure of aqueous interfaces, density profiles, and superficial dissolution are described. Most notably, hydroxyapatite-water interfaces exhibit facet-specific and pH-specific density profiles. Water stabilizes (010) facets better than (001) facets in a pH range from 10 to 5, consistent with preferred nanocrystal shape and growth in the (001) direction observed in experiment. Towards lower pH values, increasing penetration of water into sub-surface layers is observed, water density profiles flatten, and superficial dissolution occurs. The force field and surface models can be applied to elucidate mechanisms of mineralization as well as specific binding and assembly of peptides, polymer, and drugs. Extensions to substituted and defective apatites as well as to other calcium phosphate phases are feasible.

骨与牙齿的矿化过程涉及生物分子与羟基磷灰石（hydroxyapatite）之间的相互作用。当前实验室技术难以在1至100纳米尺度下解析相关的复杂界面与过程，而既往用于原子模拟（atomistic simulations）的磷灰石模型在化学键表征、表面化学及界面相互作用的刻画上均存在局限。
本研究提出了一套精准的力场（force field）与pH分辨的羟基磷灰石表面模型，可定量复现与实验相符的化学键、结构、表面、界面及力学性质，其精度较早期模型提升数个量级，可实现无机-生物组装过程的定量监测。
该力场已整合至AMBER、CHARMM、CFF、CVFF、DREIDING、GROMACS、INTERFACE、OPLS-AA及PCFF力场套件中，支持对任意组分与离子强度的磷灰石-生物体系开展写实模拟。
相较于实验结果，该模型可精准复现多项关键性质：晶格常数（偏差<0.5%）、红外光谱、解理能、水中浸没能（偏差<5%）及弹性常数（偏差<10%）。矿物、水与有机化合物间的相互作用通过标准组合规则表征，无需额外可调参数，即可实现定量精度。
基于大量实验数据，本研究构建了常见(001)、(010)、(020)及(101)晶面（facets）与纳米晶体（nanocrystals）的pH依赖型表面模型。研究还揭示了表面与浸没能、水界面结构、密度分布及表面溶解的新机制。
尤为值得注意的是，羟基磷灰石-水界面呈现晶面特异性与pH特异性的密度分布特征。在pH 10至5的范围内，水对(010)晶面的稳定作用优于(001)晶面，这与实验中观测到的纳米晶体优先沿(001)方向生长的形貌一致。随着pH值降低，水向亚表层的渗透逐渐增强，水密度分布趋于平缓，并发生表面溶解现象。
该力场与表面模型可用于阐明矿化机制，以及肽类、聚合物与药物的特异性结合与组装过程。此外，将其拓展至取代型、缺陷型磷灰石及其他磷酸钙相均具有可行性。