Date of Award
Fall 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Molecular Biophysics and Biochemistry
First Advisor
Hammes-Schiffer, Sharon
Abstract
All biological processes occur in aqueous solution. Water dictates biomolecular structure, is responsible for a large portion of the free energy of ligand binding, and participates structurally in protein-protein interactions. However, few experimental techniques can probe the biomolecular hydration shell and its diverse environments. Chirality-sensitive vibrational sum frequency generation spectroscopy (chiral SFG) is a powerful technique that probes hydration shell water. The work presented here clarifies the conditions required for a chiral SFG signal to emerge, identifies the water immediately neighboring a biomolecule as the source of the aqueous chiral SFG signal, and investigates the interaction between biomolecules and their hydration shell by modeling the responses of the water and biomolecule and the vibrational coupling between them. In the process, this work extends the much-used electrostatic frequency mapping method to the NH stretch of proteins and develops Voronoi tessellation methods for computationally dissecting molecular systems. Taken together, this work helps to put chiral SFG on a firm theoretical and computational footing, extending the pioneering work of Simpson, Skinner, Corcelli, Knoester, Jansen, and Morita.
Recommended Citation
Konstantinovsky, Daniel, "Probing Diverse Biological Systems and their Hydration Shells by Modeling Chiral Sum Frequency Generation Spectroscopy" (2023). Yale Graduate School of Arts and Sciences Dissertations. 1121.
https://elischolar.library.yale.edu/gsas_dissertations/1121
