(169bm) Protein Mediated Calcite Nucleation and Growth Characterized with Molecular Dynamics Simulations

Biomineralization is a process by which organisms produce complex and multifunctional inorganic materials via directed crystal growth. This process displays a level of hierarchical order and control beyond what is capable with contemporary materials design and therefore presents an exciting opportunity for study. Materials formed through biomineralization are ubiquitous in nature; one of the most common and well-studied examples is the protein-mediated formation of carbonate shells by marine animals. Advancements in protein design have resulted in the discovery of proteins that can imitate complex processes such as carbonate shell formation. A more complete understanding of the molecular-level interactions between proteins and surfaces that regulate these biomineralization processes would provide insight necessary for better predictive design. One model that could provide such insight is the protein mediated growth of calcium carbonate, and in particular the growth of the most stable polymorph of calcium carbonate: calcite. Physics based simulations offer a particularly attractive opportunity to characterize these mechanisms at the atomic scale. In this work, we use classical Molecular Dynamics and Monte Carlo simulations investigate the mechanism by which two de novo designed proteins, FD31 and DHR49, mediate and direct calcite nucleation and growth. The results of these simulations provide insight into 1) the specific residues that promote nucleation and binding, and 2) the role of water in mediating these interactions. Finally, we hypothesize a mechanism by which these proteins direct calcite growth. This work provides insight into the mechanisms of biomineralization and presents potential avenues for improvement of de novo protein design.