Vibrational Sum Frequency Generation Spectroscopy of Chiral Water Superstructures Around Protein
Date of Award
Doctor of Philosophy (PhD)
Protein function depends on protein structure which depends on protein hydration. This dissertation presents a body of work that establishes a fundamental concept in the study of hydration of proteins at interfaces: an assembly of achiral water molecules can form a chiral hydration shell around protein. Chiral sum frequency generation (SFG) spectroscopy—a chiral optical vibrational spectroscopy that is sensitive to the macroscopic chirality of macromolecular and supermolecular structures at interfaces—is applied to study an amphiphilic peptide that self-assembles into antiparallel beta-sheets at interfaces. This dissertation provides experimental and computational evidence supporting the existence of a chiral water superstructure around the antiparallel beta-sheet protein secondary structure. Chiral SFG studies of the structures, dynamics, and hydration of the antiparallel beta-sheet at the air-water, air-glass, and air-quartz interfaces are presented. Using isotopic substitution, isotopic dilution, H2O-D2O exchange kinetics, and phase-sensitive heterodyne chiral SFG, the O-H stretching modes of water molecules are shown to contribute to the chiral SFG vibrational spectrum of the antiparallel beta-sheet protein. Because water molecules are achiral, their detection by chiral SFG implies formation of a chiral water superstructure around the protein. The chirality of the water superstructure is demonstrated to correlate with the chirality of the protein due to hydrogen bonding interactions between the hydration shell water molecules and the protein backbone. In this way, the protein acts as a molecular template that determines the chiral architecture of the water superstructure. Implications of the existence of chiral water superstructures around proteins are considered, including potential consequences for protein structures, dynamics, stability, and biomolecular interactions. A potential role for chiral water superstructures in the emergence of biological homochirality is proposed. The major conclusion of this dissertation, that a protein can organize water molecules into a chiral hydration shell, suggests new perspectives on why water is necessary for biological life.
Perets, Ethan Alexander, "Vibrational Sum Frequency Generation Spectroscopy of Chiral Water Superstructures Around Protein" (2022). Yale Graduate School of Arts and Sciences Dissertations. 645.