Dissertations, Theses, and Capstone Projects

Date of Degree

9-2025

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Chemistry

Advisor

Nicolas Giovambattista

Advisor

Xi Chen

Committee Members

Gustavo Lopez

Donna McGregor

Subject Categories

Computational Chemistry | Materials Chemistry

Keywords

peptide crystals, hydration, water-responsive

Abstract

Water plays a crucial role in shaping the behavior and function of biomolecules across the liquid, supercooled, and glassy states. This thesis presents a dual approach combining computational simulations and experimental investigations to explore the influence of water on biomolecular systems, particularly peptide-based materials. We employ molecular dynamics simulations to study the hydration-dependent structural dynamics of homopolymer peptides. Simulations were carried out across a range of temperatures and pressures to analyze changes in hydration and structural stability, shedding light on the behavior of peptides under supercooled and glassy conditions. These studies are especially relevant for understanding biomolecular stability in cryopreservation. The second part investigates water-responsive (WR) peptide crystals through experimental characterization. Chapter 4 focuses on the tripeptide HYF, exploring how its WR actuation is influenced by the presence of deuterium oxide (D2O). Chapter 5 extends this work to a new set of hydrophobic dipeptides: LA, LG, AV, VA, IV and VF. Crystallization trials under varied conditions yielded new polymorphs of VF. PXRD and AFM measurements confirmed their structural transitions in response to changes in humidity, while the other candidates exhibited no response. This work reveals that WR behavior correlates with specific features such as solvent-accessible cavities and is sensitive to packing motifs. This thesis highlights the critical role of water in modulating peptide behavior at the molecular and macroscopic scales and provides insights for developing cryopreservation strategies and new functional materials.

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