Mirror-image antiparallel β-sheets organize water molecules into superstructures of opposite chirality

Significance The structure and function of biomacromolecules depend on water structures in the hydration shell. We perform experiments and computations to examine the water molecules around an antiparallel β-sheet. Our experiments show that the sign of chiral optical responses of water reverses when the β-sheet is an ( l -) or a ( d -) enantiomer. Molecular modeling reveals a chiral topology of water assembled around the β-sheet. These results suggest that mirror-image proteins organize water molecules into supermolecular structures of opposite chirality. Hence, a complete description of biomacromolecular chirality must include the surrounding water molecules. This finding invites a new line of inquiry about the role of water in chiral selectivity of biomolecular interactions and the molecular origins of homochirality in the biological world.