EFFECT OF ACIDIC BIOMOLECULES ON ION SOLVATION DURING CALCIFICATION: A MOLECULAR DYNAMICS STUDY

Macromolecules rich in aspartic acid (Asp) are known to play a role in biomineral morphology and phase selection, and have been shown to greatly enhance the growth kinetics of calcite. Anecdotal evidence suggests that a critical function of these biomolecules lies in their ability to modify solvent properties in the local environment of crystal nucleation and growth. To test the idea that biomolecular species modulate ion hydration environments, we investigated the influence of acidic amino acids and dipeptides on the solvation of cations using molecular dynamics (MD). Each simulation monitored the solvation state of a divalent cation (Mg, Ca, Sr) in the presence of an acidic amino acid or dipeptide (Asp, AspAsp, AspLeu). Calculated radial distribution functions were used to determine the structure of the primary hydration shell at various cation-organic separation distances. Free energy profiles for the interaction of solvated cations with carboxylate moities were generated by umbrella sampling and the weighted histogram analysis method (WHAM). Simulations employed the LAMMPS software with the TIP3P water model, CHARMM22 force field, and Åqvist ion-water potentials.

We show the hydration environments of Ca and Sr are perturbed as the ions approach the negatively charged amino acid carboxylate groups. Complexation of Ca and Sr by carboxylate oxygen atoms results in a decreased total first shell coordination number relative to the ions in bulk water. The primary solvation shell of Mg is largely unchanged by organics until the physical replacement of a water molecule with a caboxylate oxygen, which appears to be highly unfavorable energetically. Proximity to organics has no effect upon ion-oxygen distances of waters in the first hydration sphere. The calculated energy barrier for Ca association with the biomolecules is very small (a few kT). For Sr, sterics appear to prevent the larger ion from taking the same path of approach as Ca, resulting in a larger energy cost. The findings suggest origins of biomolecule-specific influences on nucleation and growth of calcium carbonates and phosphates and the roles of matrix organic molecules in biomineral phase selection.