Molecular Driving Forces in the Self-Association of Silaffin Peptide R5 from MD Simulations

The 19-residue silaffin-R5 peptide has been widely studied for its ability to precipitate uniform SiO2 particles through mild temperature and pH pathways, in the absence of any organic solvents. There is consensus that post-translational modification (PTM) of side chains has a large impact on the biomineralization process. Thus, it is imperative to understand the precise mechanisms that dictate the formation of SiO2 from R5 peptide, including the effects of PTM on peptide aggregation and peptide-surface adsorption. In this work, we use molecular dynamics (MD) simulations to study the aggregation of R5 dimer with multiple PTMs, with the presence of different ions in solution. Since this system has strong interactions with deep metastable states, we use parallel bias metadynamics with partitioned families to efficiently sample the different states of the system. We find that peptide aggregation is a prerequisite for biomineralization. We observe that the electrostatic interactions are essential in the R5 dimer aggregation; for wild type R5 that only has positively charged residues, phosphate ions HPO42- in the solution form a bridge between two peptides and are essential for peptide aggregation. Alternatively, the post translational modification phosphorylation, which renders neutral serine residues negative, enables R5 to aggregate without phosphate ion. The extent of phosphorylation and location of phosphorylated residues on R5 peptide results in different behavior and extent of aggregation - the aggregation trend of R5 peptide that we observe is in line with SiO2 precipitation observed in previous experimental studies, proving that peptide aggregation is a prerequisite for biomineralization.