Computational Studies of Bio-Inspired Synthetic Random Heteropolymers

Abstract

Biological heteropolymers, such as proteins and nucleic acids, work together to execute the vast suite of tasks which ultimately enable life. These capabilities, particularly enzymatic function, are incredibly attractive for developing sustainable materials, removing pollutants and contaminants, designing advanced nanomedicines, and countless other applications. However, as proteins typically denature and lose functionality in non-physiological conditions, harnessing their activity in processing steps or end applications which require foreign environments proves difficult. Amphiphilic synthetic polymers can provide a bio-inspired means for augmenting, and even mimicking, bio-macromolecular function. A four component methacrylate-based random heteropolymer (RHP) system has been demonstrated to be especially promising as an easily scalable and broadly effective option for protein-stabilization and protein-mimicry. The statistical distribution of random chains makes analysis of particular molecules and motifs challenging experimentally. In this thesis, we use atomistic molecular dynamics simulations to perform nanoscale characterization of individual sequences to provide insight into how such synthetic polymers behave. We draw from random heteropolymer theory and experimentation to develop a set of computational studies which lead to a comprehensive view of how the polymers assemble, move, and interact in solution. First, we focus on the structure and dynamics of RHPs in aqueous solution, investigating what drives their assembly. We found the polymers to have multiple dynamic modes and heterogeneous surfaces in water, properties which scale predominantly with composition rather than particular sequence motifs. We then study the impact of solution environment, examining polymer response to varied solvent properties. Modulation of electrostatic and polar interactions showed strong environmental-dependence on RHP assembly with significant activation barriers to remodeling upon altering solvent. Finally, we characterize RHP interactions with other macromolecules, small molecules, and interfaces. These studies demonstrate that such interactions alter not only the driving forces to assembly, but can also introduce high energy interfaces that may stimulate changes in polymer conformation. Our analyses, leveraging techniques from both polymer physics and protein sciences, enable predictable modification and processing of synthetic polymer assemblies. As native proteins and nucleic acids are, themselves, heteropolymers, this thesis also provides a synthetic perspective that relays behavioral relationships back to the biomolecules that inspire it.