(647c) Designing Sequence Controlled Polymers for Biomineralization: A Predictive Approach Using Molecular Dynamics Simulations

Benign synthesis methods to manufacture inorganic nanomaterials such as silica and titania can minimize the adverse environmental impact caused by current synthesis techniques that require extreme temperature and pH conditions. Organisms such as diatoms and sponges produce intricate nanostructures in water at ambient conditions through a process known as biomineralization. To this end, Silaffin, a naturally occurring protein that regulates and controls the silica biomineralization process in diatoms has been studied extensively. The 19 amino acid segment of Silaffin, R5 (SSKKSGSYSGSKGSKRRIL), shows similar in vitro nano-silica formation activity as the parent protein, and has therefore been extensively employed as a model peptide in many experiments and simulations to elucidate the driving forces of biomineralization. It has been proven that for R5 to facilitate mineral precipitation in solution, either post translational modification (PTM) in the form of phosphorylation of the serine sidechain, or the presence of phosphate ions in solution is required. Recent work in our group established that a strong indicator of R5 systems to undergo biomineralization was their ability to form dimers with positive charges exposed, which was observed in both systems mentioned above. On the other hand, R5 systems that do not precipitate silica were found to not dimerize with positive charges on their periphery.

Peptoids, a class of N-glycine substituted peptidomimetic polymers have been successfully employed to produce gold nanoparticles as well as dentin tubules in vitro due to the ability to precisely define peptoid sidechain sequences to mimic their peptide or protein counterpart. Additionally, the absence of backbone hydrogen bonds in peptoids enables explicit interactions through the side chains, leading to highly predictable macroscopic functions through a controlled microscopic structure. Motivated by the fact that R5 is an intrinsically disordered peptide without the backbone significantly impacting its functionality, we designed a peptoid mimic that bears the same sidechain sequence as R5 (referred to as Rp5), to test the conditions under which it may undergo biomineralization. We study Rp5 under five distinct conditions (1) wild type Rp5 (2) Rp5 with phosphate ions (3) Rp5 with phosphorylation on Ser1 (4) Rp5 with phosphorylation on Ser14 (5) globally phosphorylated Rp5. Enhanced sampling using Parallel Bias Metadynamics with Partitioned Families (PBMetaD-PF) was employed to ensure convergence of the energy landscape. Free energies of dimerization, and conformation of the dimers was calculated. This work can inform the rational design of sequence-controlled polymers for biomineralization.