Challenges in studying the liquid-to-solid phase transitions of proteins using computer simulations.

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Membraneless organelles (biomolecular condensates) are crucial for cellular functions.
• Their dysregulation is linked to diseases like cancer and neurodegeneration.
• Liquid-liquid phase separation (LLPS) is a key mechanism for condensate formation.

Purpose of the Study:

• To review biophysical studies on liquid-to-solid phase transitions in proteins.
• To summarize computational models for protein aggregation and phase separation.
• To discuss computational approaches for understanding liquid-to-solid transitions.

Main Methods:

• Review of recent biophysical experimental studies.
• Summary of existing computational models.
• Discussion of advanced computational approaches.

Main Results:

• Biophysical studies reveal molecular mechanisms of liquid-to-solid transitions.
• Various computational models exist for studying protein aggregation and LLPS.
• Emerging computational methods capture the physics of liquid-to-solid transitions.

Conclusions:

• Understanding liquid-to-solid transitions in biomolecular condensates is crucial for disease research.
• Computational models offer valuable insights complementary to experimental approaches.
• Further development of computational methods is needed to fully elucidate these transitions.