(223al) Molecular Scale Insights of the Structure Selective Growth of Bionanostructures: A Coarse-Grained and Metadynamics Based Study of Biosilica

In recent years there has been increasing interest in using computational tools to understand the bio/nano interface.  Examples include protein adsorption, interfacial biocatalysis, and templated growth of bionanostructures such as biosilica. This poster will present a study of how various computational tools can be used to study molecular scale driving forces in peptide aggregation as well as how small peptide aggregates with identical composition but different structure template the growth of unique mesoscale bionano morphologies. The LK peptides are short amino acid sequences composed of leucine and lysine that adopt sequence-dependent secondary structure (e.g., alpha helix, beta, 3₁₀ helix). These peptides have been well known to facilitate the growth of biosilica composites when placed in saturated solutions of silicon dioxide. Interestingly, it has recently been shown that the choice of LK peptide can dramatically change the resultant silicon dioxide nanoparticles. Guided by the underlying hypothesis that fine differences between small peptide aggregates are driving the unique changes in the morphology, we have sought to use molecular simulation to better understand this process. We have conducted coarse grained molecular dynamics simulations and additionally applied the metadynamics technique to study free energy landscapes of LK peptide aggregates.

We began our simulations by converting atomistic representations of our systems of randomly oriented LK peptides to MARTINI coarse grained (CG) models with explicit polarizable coarse grained water. By conducting molecular dynamics simulations with metadynamics, we were able to effectively explore and uncover the free energy of the aggregation of these peptides. Upon inspection of the free energy surface, it was clear that the systems have several metastable minima that would not be readily overcome in normal molecular dynamics systems and that enhanced sampling techniques are necessary to fully explore similar systems. Additional simulations used reverse coarse-graining to study the stability of the various aggregates at atomic resolution. Starting from a well-known scientific question about the preference of LK alpha-14 peptides to form tetrameric aggregates, we proceeded to address the question of how the different aggregates interact with amorphous silica nanoparticles.  Finally, we used all of the studies at atomic and coarse resolution to quantitatively estimate the degree to which the simple CG models accurately capture the essential physical interactions in corresponding atomistic models.