Detecting the First Hydration Shell Structure around Biomolecules at Interfaces

Abstract

Understanding the role of water in biological processes remains a central challenge in the life sciences. Water structures in hydration shells of biomolecules are difficult to study in situ due to overwhelming background from aqueous environments. Biological interfaces introduce additional complexity because biomolecular hydration differs at interfaces compared to bulk solution.Here, we perform experimental and computational studies of chiral sum frequency generation (chiral SFG) spectroscopy to probe chirality transfer from a protein to the surrounding water molecules. This work reveals that chiral SFG probes the first hydration shell around the protein almost exclusively. We explain the selectivity to the first hydration shell in terms of the asymmetry induced by the protein structure and specific protein−water hydrogen-bonding interactions. This work establishes chiral SFG as a powerful technique for studying hydration shell structures around biomolecules at interfaces, presenting new possibilities to address grand research challenges in biology, including the molecular origins of life.

Design of an Electrostatic Frequency Map for the NH Stretch of the Protein Backbone and Application to Chiral Sum Frequency Generation Spectroscopy

“…Simpson and co-workers have established symmetry-based chiral SFG theory to describe vibrational chiral SFG in the absence of electronic resonance as surface-selective in uniaxial ( C ∞ ) systems. , Over the past decade, chiral SFG has developed into a powerful technique for probing the secondary structure of chiral biomacromolecules at interfaces and the solvent around them. ,− There are aspects of chiral SFG that are not yet understood. For example, we do not have a straightforward mapping from chiral phase (signal sign) to dipole orientation, unlike in conventional (achiral) SFG.…”

Dynamic Electric Field Alignment Determines the Water Rotational Motion around Protein

“…20 Similarly, for water outside the first hydration layer, the tendency of water dipoles to be aligned with the electric field is concluded as an intrinsic property of bulk water. 21,22 In the state-of-theart experimental and computational studies of chiral sum frequency generation (chiral SFG) spectroscopy, 26 relative to that beyond provides the chiral SFG sensitivity to the water in the first hydration shell. The above investigations mainly paid attention to the static alignment (the angle) of water dipole to the electric field generated from protein but not to its effect on the dynamics of water dipole.…”

“…With the recent advancement of the Voronoi analysis of water shells, the long-range ordering influence of the protein on the structure of solvent distant from the protein was further demonstrated. − The parallelization of water dipole to the electric field outside the first hydration layer was implied to be achieved by water–water interactions from shell to shell instead of by the dielectric response of the solvent to the decaying electric field of the protein . Similarly, for water outside the first hydration layer, the tendency of water dipoles to be aligned with the electric field is concluded as an intrinsic property of bulk water. , In the state-of-the-art experimental and computational studies of chiral sum frequency generation (chiral SFG) spectroscopy, Konstantinovsky et al determined that the ordering of water dipoles extends 30–40 Å away from the protein and gradually fades into random arrangements beyond 40 Å. Besides, the much less symmetrical ordering within the first hydration layer relative to that beyond provides the chiral SFG sensitivity to the water in the first hydration shell.…”

Biomolecular Chirality Is Imprinted on One Layer of Hydration Water

“…A chiral SFG technique together with the findings disclosed by Konstantinovsky and co-workers 7 ensures that the chirality near the DNA arises from the first hydration shell, 9 allowing the mapping of the hydrated water molecules to the DNA structure. Furthermore, by applying the chiral SFG technique to monitoring the protein docking process, one can see how proteins are dehydrated by the docking process.…”

“…The work in ref highlights the strength of combining experiments with advanced SFG spectral simulation. The simulations reproduce both the achiral and the chiral response.…”