Raman Dissection of Water-Interaction Coupling in Condensate-Relevant Peptides.

Area of Science:

• Biophysics
• Molecular Biology
• Chemical Physics

Background:

• Biomolecular condensates form via liquid-liquid phase separation.
• Noncovalent interactions of intrinsically disordered proteins (IDPs) and nucleic acids drive condensate formation.
• The role of water in modulating these interactions within condensates is unclear.

Purpose of the Study:

• To investigate how water influences molecular interactions relevant to biomolecular condensate formation.
• To understand the role of hydration in the behavior of IDPs and peptides.
• To elucidate the physicochemical basis of condensate formation.

Main Methods:

• Time-resolved Raman spectroscopy was used to study amino acids and IDP-derived peptides.
• Molecular crowding was simulated via controlled solution evaporation.
• Changes in molecular vibrational modes and water structure were tracked.

Main Results:

• Distinct molecular responses were observed based on interaction type (hydrogen bonding vs. hydrophobic).
• Hydrogen-bonding peptides retained more tetrahedral water.
• Hydrophobic peptides exhibited stepwise water depletion, affecting backbone and side-chain behavior.

Conclusions:

• Hydration significantly influences the behavior of condensate-relevant molecules.
• Water structure (tetrahedral vs. distorted) is differentially retained based on interaction type.
• Findings provide molecular insights into the physicochemical drivers of biomolecular condensate formation.