(194c) Peptide Adsorption on Hydroxyapatite Surfaces and Implications on Shape and Mineralization: Impact of Sequence and Electrolyte pH

Hydroxyapatite (HAP) is a common calcium phosphate phase in teeth and bone, however, details of its formation and dissolution have remained difficult to understand in atomic detail. In biomimetic laboratory synthesis, the peptide sequence MLPHHGA (HABP1) derived from phage display leads to the formation of plate-like HAP nanocrystals at pH 7 with a lower initial nucleation rate compared to using no peptides or a control sequence NPGFAQA (HABP2) that is not active in binding and mineralization. Recent developments of accurate apatite models in the Interface force field (IFF) allow pH sensitive simulations of mineral precursors, nanocrystals, and biointerfaces (CHARMM-IFF, AMBER-IFF) in atomic resolution. Here we describe the molecular interaction of HABP1 and HABP2 with apatite surfaces at pH values of 5, 7, and 10 for all common crystal surfaces including the (001) basal plane, the prismatic (010) and (020) surfaces, as well as (101) surfaces at the tip of HAP crystallites. HABP1 shows much stronger adsorption on the HAP (101) and (020) surfaces compared to (001) and (010) surfaces. HABP1 in solution also shows a high affinity to calcium ions which is likely to slow down the nucleation rate of hydrogen phosphate precursors to form apatite. The differences in the computed adsorption free energy of HABP1 on each facet of HAP are consistent with the observed of plate-like morphology in experiment at pH 7, and specific to the chosen pH value. The control peptide sequence NPGFAQA (HABP2) does not exhibit strong binding performance to any facet of HAP, and neither a strong affinity to calcium ions in solution, which is in good agreement with the experimental observation of a sphere-like morphology of biomimetically grown HAP and a higher initial nucleation rate. The findings show that the new molecular models and simulations using CHARMM-IFF are of predictive quality and can be used for rational biomaterials design.