Handy water: Chiral superstructures around peptide β-sheets

Abstract

Water is a key component of biological systems. Traditionally, water is considered as the background against which biology evolves. However, recently, it is becoming apparent that water is very much an essential part of the system. One could even ask to what extent water determines the structure of proteins, membranes, DNA, and the more complex biomachinery that is composed of multiple compounds. To answer this question, it is important to understand how the hydration shell of a biomolecule responds to its structural changes. Chirality (or handedness) is one of the most fundamental aspects of biomolecular structure. Two molecular groups are chiral when they have the same chemical structure but are each other’s mirror image. Amino acids in proteins are chiral, and although they can exist as left (L-) and right-handed (D-) mirror images, only L-enantiomers are found in nature. In contrast, sugars and DNA occur only in D-form. Macromolecules constructed from chiral building blocks form either exclusively Lor D-structures. The vast majority of biological reactions in aqueous environments are fine-tuned for their speed and accuracy by using chiral selectivity. Determining the structural properties of water around chiral biomolecules is therefore important to understand the complexity of life itself. However, experimentally measuring the structure of water in contact with a biomolecule or larger molecular assemblies is a challenging task. In PNAS Perets et al. (1) implement an elegant approach that combines interferometric chiral sum frequency generation (SFG) spectroscopy, isotopic exchange experiments, and molecular dynamics (MD) simulations to understand the relationship between peptide β-sheets and their hydrating water. (L-) and (D-) antiparallel peptide β-sheets are demonstrated to impart their chirality to adjacent water molecules, leading to chiral superstructures of water around peptides that extend for approximately five hydration layers. When two laser pulses of infrared and visible frequencies are spatially and temporally overlapped on a quartz window that is in contact with an aqueous solution of the strongly amphiphilic peptides, sum frequency photons are generated exclusively from regions lacking centrosymmetry. At the interface between the biomolecules and water, symmetry is necessarily broken. The symmetry requirements of SFG further make it an excellent tool to probe chiral ordering of various biomolecules at interfaces (2). Even though the majority of chiral SFG studies were done with molecules possessing intrinsic chirality, it is in theory possible that a chiral interface orders an achiral molecule into a chiral extended superstructure, which can potentially generate chiral SF photons (3). MD simulations have predicted that the local variations in DNA–water hydrogen bonding interactions combined with the spatial confinement imposed by the Fig. 1. Revealing chiral water superstructures using interferometric SFG. Hydrated films of antiparallel peptide β-sheet assemblies are formed on the surface of α-quartz. The detected chiral SFG electromagnetic field is added to that of α-quartz, leading to intensities I1 and I2. I1 and I2 are measured for two different orientations of the α-quartz crystal. I1 − I2 provides the direction of the electromagnetic field which reports on the up/down orientation of dipoles. The sketched spectra showmirror-image signals observed for Lvs. D-enantiomers. The illustration at the bottom right depicts the checkerboard-like pattern of water dipole orientations that form the chiral structure, revealed fromMD simulations by Perets et al. (1).