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Abstract
Whether in designing novel materials or simply sustaining basic biological function, the dynamics of biological and bio-inspired macromolecules are key in multiple processes impacting daily life. These dynamics involve a variety of scenarios, including the self-assembly of biomacromolecules, their native dynamics within living cells, and their use in functional materials in order to bind with specific foreign species. In this dissertation, a multitude of tools in the molecular simulation arsenal are deployed to investigate biomacromolecule dynamics in all three scenarios. We begin by using atomistic molecular dynamics to study early-stage aggregation of human islet amyloid polypeptide (hIAPP), an amyloid-forming protein implicated in type II diabetes. By applying the finite temperature string method, we identify potential pathways for the first stages of self-assembly of hIAPP into dimers, as well as relevant aggregation intermediates and their relative stabilities. We then extend our investigation of hIAPP to the formation of trimers, for which we examine multiple possible aggregation mechanisms and study their fundamental mechanistic and thermodynamic differences. We then consider the design of a peptide amphiphile, consisting of a polypeptide chain attached to an alkyl chain that drives self-assembly. We examine the dynamics and energetics of a candidate peptide amphiphile binding to phosphate, which may be harnessed for the sustainable sequestration of phosphate from wastewater. Finally, we proceed to apply a combination of molecular dynamics and nonlinear manifold learning techniques to identify the key dynamical motions of the nucleosome, another biological macromolecular system consisting of 147 base pairs of DNA wrapped around a complex of eight histone proteins, whose sequence-dependent behavior affects critical functions including gene expression and DNA replication.