Role of desolvation on biomolecular liquid-liquid phase separation.

Incorporating desolvation effects into coarse-grained models reveals that desolvation energetics significantly influence the thermodynamics and kinetics of biomolecular liquid-liquid phase separation.

• Why it matters: Understanding the role of water-mediated desolvation is crucial because it impacts the accuracy of models used to study biomolecular condensates, which are vital for cellular organization and linked to disease processes.
• What they did: The authors developed a desolvation-aware implicit-solvent coarse-grained model by adding residue-level desolvation terms based on all-atom simulations and experimental data, then applied it to intrinsically disordered proteins.
• The result: The model shows that desolvation reshapes the phase diagram, correlates linearly with conformational expansion during phase transition, and modulates chain mobility and transient kinetics, enhancing mechanistic insights into LLPS.