Chirality-selective vibrational sum frequency generation (chiral SFG) spectroscopy has emerged as a powerful technique for the study of biomolecular hydration water due to its sensitivity to the induced chirality of the first hydration shell. Thus far, water O–H vibrational bands in phase-resolved heterodyne chiral SFG spectra have been fit using one Lorentzian function per vibrational band, and the resulting fit has been used to infer the underlying frequency distribution. Here, we show that this approach may not correctly reveal the structure and dynamics of hydration water. Our analysis illustrates that the chiral SFG responses of symmetric and asymmetric O–H stretch modes of water have opposite phase and equal magnitude and are separated in energy by intramolecular vibrational coupling and a heterogeneous environment. The sum of the symmetric and asymmetric responses implies that an O–H stretch in a heterodyne chiral SFG spectrum should appear as two peaks with opposite phase and equal amplitude. Using pairs of Lorentzian functions to fit water O–H stretch vibrational bands, we improve spectral fitting of previously acquired experimental spectra of model β-sheet proteins and reduce the number of free parameters. The fitting allows us to estimate the vibrational frequency distribution and thus reveals the molecular interactions of water in hydration shells of biomolecules directly from chiral SFG spectra.
Biomolecular hydration is fundamental to biological functions. Using phase-resolved chiral sum-frequency generation spectroscopy (SFG), we probe molecular architectures and interactions of water molecules around a self-assembling antiparallel β-sheet protein. We find that the phase of the chiroptical response from the O-H stretching vibrational modes of water flips with the absolute chirality of the (
- Award ID(s):
- 1905169
- NSF-PAR ID:
- 10206064
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 117
- Issue:
- 52
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- p. 32902-32909
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
-
more » « less
Experimental methods capable of selectively probing water at the DNA minor groove, major groove, and phosphate backbone are crucial for understanding how hydration influences DNA structure and function. Chiral-selective sum frequency generation spectroscopy (chiral SFG) is unique among vibrational spectroscopies because it can selectively probe water molecules that form chiral hydration structures around biomolecules. However, interpreting chiral SFG spectra is challenging since both water and the biomolecule can produce chiral SFG signals. Here, we combine experiment and computation to establish a theoretical framework for the rigorous interpretation of chiral SFG spectra of DNA. We demonstrate that chiral SFG detects the N–H stretch of DNA base pairs and the O–H stretch of water, exclusively probing water molecules in the DNA first hydration shell. Our analysis reveals that DNA transfers chirality to water molecules only within the first hydration shell, so they can be probed by chiral SFG spectroscopy. Beyond the first hydration shell, the electric field-induced water structure is symmetric and, therefore, precludes chiral SFG response. Furthermore, we find that chiral SFG can differentiate chiral subpopulations of first hydration shell water molecules at the minor groove, major groove, and phosphate backbone. Our findings challenge the scientific perspective dominant for more than 40 years that the minor groove “spine of hydration” is the only chiral water structure surrounding the DNA double helix. By identifying the molecular origins of the DNA chiral SFG spectrum, we lay a robust experimental and theoretical foundation for applying chiral SFG to explore the chemical and biological physics of DNA hydration.
-
Defined based on geometric concepts, the origin of biological homochirality including the single handedness of key building blocks, D-sugars and L-amino acids, is still heavily debated in many ongoing research endeavors. Origin aside, transmission and amplification of chirality across length scales are likely essential for the predominance of one handedness over the other in chiral systems and are attracting an unabated interest not only in biology but also in material science. To offer a measure for chirality and through-space chirality transfer, we here provide a report on recent progress toward the development of a suitable approach for an a priori prediction of chirality “strength” and efficacy of chirality transfer from a chiral solute to an achiral nematic solvent. We achieve this by combining an independently calculated, suitable pseudoscalar chirality indicator for the solute with another, independently calculated scalar solute–solvent shape compatibility factor. In our ongoing pursuit to put this approach to the test, we are advancing and refining a versatile experimental platform based on achiral gold nanoparticle cores varying in size, shape, and aspect ratio capped with monolayers of chiral molecules or on intrinsically chiral cellulose nanocrystals that serve as chiral solutes in an achiral nematic liquid crystal phase acting as a reporter medium. The pitch of the ensuing induced chiral nematic liquid crystal phase ultimately serves as a reporter medium that allows us to experimentally quantify and compare chirality and efficacy of chirality transfer.more » « less
-
Following the seminal theoretical work on the pleated β-sheet published by Pauling and Corey in 1951, the rippled β-sheet was hypothesized by the same authors in 1953. In the pleated β-sheet the interacting β-strands have the same chirality, whereas in the rippled β-sheet the interacting β-strands are mirror-images. Unlike with the pleated β-sheet that is now common textbook knowledge, the rippled β-sheet has been much slower to evolve. Much of the experimental work on rippled sheets came from groups that study aggregating racemic peptide systems over the course of the past decade. This includes MAX1/DMAX hydrogels (Schneider), L/D-KFE8 aggregating systems (Nilsson), and racemic Amyloid β mixtures (Raskatov). Whether a racemic peptide mixture is “ripple-genic” ( i.e. , whether it forms a rippled sheet) or “pleat-genic” ( i.e. , whether it forms a pleated sheet) is likely governed by a complex interplay of thermodynamic and kinetic effects. Structural insights into rippled sheets remain limited to only a very few studies that combined sparse experimental structural constraints with molecular modeling. Crystal structures of rippled sheets are needed so we can rationally design rippled sheet architectures. Here we report a high-resolution crystal structure, in which ( l , l , l )-triphenylalanine and ( d , d , d )-triphenylalanine form dimeric antiparallel rippled sheets, which pack into herringbone layer structures. The arrangements of the tripeptides and their mirror-images in the individual dimers were in excellent agreement with the theoretical predictions by Pauling and Corey. A subsequent mining of the PDB identified three orphaned rippled sheets among racemic protein crystal structures.more » « less
-
more » « less
Abstract Assemblies of racemic β‐sheet‐forming peptides have attracted attention for biomedical applications because racemic forms of peptides can self‐associate more avidly than do single enantiomers. In 1953, Pauling and Corey proposed “rippled β‐sheet” modes of H‐bond‐mediated interstrand assembly for alternating L‐ and D‐peptide strands; this structural hypothesis was complementary to their proposal of “pleated β‐sheet” assembly for L‐peptides. Although no high‐resolution structure has been reported for a rippled β‐sheet, there is strong evidence for the occurrence of rippled β‐sheets in some racemic peptide assemblies. Here we compare propensities of peptide diastereomers in aqueous solution to form a minimum increment of β‐sheet in which two antiparallel strands associate. β‐Hairpin folding is observed for homochiral peptides with aligned nonpolar side chains, but no β‐hairpin population can be detected for diastereomers in which one strand contains L residues and the other contains D residues. These observations suggest that rippled β‐sheet assemblies are stabilized by interactions between β‐sheet layers rather than interactions within these layers.
