Recalibrating the calcium trap in amino acid carboxyl groups via classical molecular dynamics simulations

In order to use classical molecular dynamics to complement experiments accurately, it is important to use robust descriptions of the system. The interactions between biomolecules, like aspartic and glutamic acid, and dissolved ions are often studied using standard biomolecular force-fields, where the interactions between biomolecules and cations are often not parameterized explicitly. In this study, we have employed metadynamics simulations to investigate different interactions of Ca with aspartic and glutamic acid and constructed the free energy profiles of Ca2+–carboxylate association. Starting from a generally accepted, AMBER-based force field, the association was substantially over and under-estimated, depending on the choice of water model (TIP3P and SPC/fw, respectively). To rectify this discrepancy, we have replaced the default calcium parameters. Additionally, we modified the σij value in the hetero-atomic Lennard-Jones interaction by 0.5% to further improve the interaction between Ca and carboxylate, based on comparison with the experimentally determined association constant for Ca with the carboxylate group of L-aspartic acid. The corrected description retrieved the structural properties of the ion pair in agreement with the original biomolecule – Ca2+ interaction in AMBER, whilst also producing an association constant comparable to experimental observations. This refined force field was then used to investigate the interactions between amino acids, calcium and carbonate ions during biogenic and biomimetic calcium carbonate mineralisation

The impact of stoichiometry on the initial steps of crystal formation: Stability and lifetime of charged triple-ion complexes

Minerals form in natural systems from solutions with varying ratios of their lattice ions, yet non-stoichiometric conditions have generally been overlooked in investigations of new formation (nucleation) of ionic crystals. Here, we investigated the influence of cation:anion ratio in the solution on the initial steps of nucleation by studying positively and negatively charged triple ion complexes and subsequent particle size evolution. Our model systems are carbonates and sulfates of calcium and barium, as it was recently shown that solution stoichiometry affects the timing and rate of their nucleation. Molecular dynamics (MD) simulations and dynamic light scattering (DLS) flow experiments show that nucleation correlates with the stability and lifetime of the initial complexes, which were significantly impacted by the cation:anion stoichiometry and ion type. Specifically, (Formula presented.) was found to have higher association constants and its lifetime was twofold longer than (Formula presented.). Similar trends were observed for (Formula presented.) and (Formula presented.). Contrastingly, for (Formula presented.), (Formula presented.) was found to have lower association constants and its lifetime was shorter than (Formula presented.). These trends in stability and lifetime follow the same asymmetrical behaviour as observed experimentally for particle formation using techniques like DLS. This suggests a causal relationship between the stability and lifetime of the initial charged complexes and the nucleation under non-stoichiometric conditions

Recalibrating the calcium trap in amino acid carboxyl groups via classical molecular dynamics simulations

In order to use classical molecular dynamics to complement experiments accurately, it is important to use robust descriptions of the system. The interactions between biomolecules, like aspartic and glutamic acid, and dissolved ions are often studied using standard biomolecular force-fields, where the interactions between biomolecules and cations are often not parameterized explicitly. In this study, we have employed metadynamics simulations to investigate different interactions of Ca with aspartic and glutamic acid and constructed the free energy profiles of Ca2+–carboxylate association. Starting from a generally accepted, AMBER-based force field, the association was substantially over and under-estimated, depending on the choice of water model (TIP3P and SPC/fw, respectively). To rectify this discrepancy, we have replaced the default calcium parameters. Additionally, we modified the σij value in the hetero-atomic Lennard-Jones interaction by 0.5% to further improve the interaction between Ca and carboxylate, based on comparison with the experimentally determined association constant for Ca with the carboxylate group of L-aspartic acid. The corrected description retrieved the structural properties of the ion pair in agreement with the original biomolecule – Ca2+ interaction in AMBER, whilst also producing an association constant comparable to experimental observations. This refined force field was then used to investigate the interactions between amino acids, calcium and carbonate ions during biogenic and biomimetic calcium carbonate mineralisation