Theses and Dissertations

ORCID

https://orcid.org/0000-0002-9166-0527

Advisor

Gwaltney, Steven

Committee Member

Fitzkee, Nick

Committee Member

Johnson, Christopher

Committee Member

Gangishetty, Mahesh

Committee Member

Emerson, Joseph

Date of Degree

12-12-2025

Original embargo terms

Visible MSU Only 1 year

Document Type

Dissertation - Campus Access Only

Major

Chemistry

Degree Name

Doctor of Philosophy (Ph.D.)

College

College of Arts and Sciences

Department

Department of Chemistry

Abstract

Biological molecules operate in environments that are heterogeneous and dynamic, which complicates the task of identifying the physical mechanisms that govern their behavior. This dissertation develops computational approaches that combine molecular dynamics and quantum chemical methods to examine how local environments shape structure, spectroscopy, and recognition across three representative systems: lipid bilayers perturbed by choline-based ionic liquids, solvatochromic dyes in ionic and mixed solvents, and G-quadruplex DNA bound to small-molecule ligands. In the membrane studies, all-atom simulations show how anion hydrophobicity and hydration state determine bilayer remodeling, ranging from lateral compression and headgroup reorientation to tail disorder and early pore formation. These atomistic insights explain how biocompatible ionic liquids modulate permeability and inform the design of safer delivery media. In the solvatochromism studies, explicit-solvent trajectories of the squaraine dye SO₃SQ are integrated with time-dependent density functional theory to resolve the structural and electrostatic contributions to spectral shifts. The workflow captures inhomogeneous broadening from ion pairing and polarization that cannot be reproduced by continuum models, creating a predictive link between spectral signatures and microenvironment distributions. In the nucleic acid studies, docking and long-timescale simulations coupled with free-energy calculations identify feasible binding modes of the porphyrin TMPyP4 to a c-MYC G-quadruplex. The results quantify the relative stability of end-stacking and intercalation, clarifying ligand recognition at atomic detail. Taken together, these projects demonstrate that environment-specific modeling is required to connect microscopic interactions with experimentally measurable properties. The protocols established here advance the predictive scope of computational chemistry and provide general strategies for studying membrane remodeling, solvatochromic response, and nucleic acid recognition in biologically relevant systems.

Sponsorship (Optional)

Supported in part by NSF OIA-2414443 (Mississippi EPSCoR E-RISE)

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