Discovery of Biomolecular Structure-Function Mechanisms with Computational Frameworks at the Nanoscale

Abstract

Biomolecular function is closely linked to the events that occur at the molecular level, which often takes place in a complex biological environment (i.e., at a complex interface). Approaches which can correlate the massive design space of biophysical and biochemical features at the nanoscale with their expressed macromolecular behavior are of fundamental interest to the field of bioinspired design. While experimental/AI approaches have successfully been applied to characterize the behavior of solution-phase proteins, there is a lack of methods which can probe interfacial phenomena of biomolecules at the same level of resolution. Increases in compute power point to simulation approaches as one avenue for advancing the frontier of biomolecular structure/function exploration at interfaces. In this dissertation, physics-based simulation frameworks were developed and applied to model interfacial peptide, protein, and peptoid systems. As a result, this work demonstrates the capability of computational molecular models to study different biological phenomena with high accuracy, providing insight to the behavior of these complex biomolecules within the areas of biomineralization, self-assembly, and enzyme catalysis.