Binding mechanism and binding free energy of amino acids and citrate to hydroxyapatite surfaces as a function of crystallographic facet, pH, and electrolytes

Journal Article · Fri Jul 23 00:00:00 EDT 2021 · Journal of Colloid and Interface Science

DOI:https://doi.org/10.1016/j.jcis.2021.07.109· OSTI ID:1981657

Hoff, Samuel E. ^[1]; Liu, Juan ^[2]; Heinz, Hendrik ^[1]

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1. University of Colorado, Boulder, CO (United States)
2. University of Colorado, Boulder, CO (United States); Dalian Maritime University (China)

Hydroxyapatite (HAP) is the major mineral phase in bone and teeth. The interaction of individual amino acids and citrate ions with different crystallographic HAP surfaces has remained uncertain for decades, creating a knowledge gap to rationally design interactions with peptides, proteins, and drugs. In this contribution, we quantify the binding mechanisms and binding free energies of the 20 end-capped natural amino acids and citrate ions on the basal (001) and prismatic (010)/(020) planes of hydroxyapatite at pH values of 7 and 5 for the first time at the molecular scale. We utilized over 1500 steered molecular dynamics simulations with highly accurate potentials that reproduce surface and hydration energies of (hkl) hydroxyapatite surfaces at different pH values. Charged residues demonstrate a much higher affinity to HAP than charge-neutral species due to the formation of superficial ion pairs and ease of penetration into layers of water molecules on the mineral surface. Binding free energies range from 0 to -60 kJ/mol and were determined with ~10% uncertainty. The highest affinity was found for citrate, followed by Asp(-) and Glu(-), and followed after a gap by Arg(+), Lys(+), as well as by His(+) at pH 5. The (hkl)-specific area density of calcium ions, the protonation state of phosphate ions, and subsurface directional order of the ions in HAP lead to surface-specific binding patterns. Amino acids without ionic side groups exhibit weak binding, between -3 and 0 kJ/mol, due to difficulties to penetrate the first layer of water molecules on the apatite surfaces. We explain recognition processes that remained elusive in experiments, in prior simulations, discuss agreement with available data, and reconcile conflicting interpretations. In conclusion, the findings can serve as useful input for the design of peptides, proteins, and drug molecules for the modification of bone and teeth-related materials, as well as control of apatite mineralization.

• Research Organization: Argonne National Laboratory (ANL), Argonne, IL (United States). Argonne Leadership Computing Facility (ALCF)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); National Science Foundation (NSF)
• Grant/Contract Number: AC02-06CH11357; DMREF-1623947; CBET-1530790; OAC 1931587; ACI-1532235; ACI-1532236
• OSTI ID: 1981657
• Journal Information: Journal of Colloid and Interface Science, Vol. 605, Issue C; ISSN 0021-9797
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Chemistry