Model for disordered proteins with strongly sequence-dependent liquid phase behavior

Area of Science:

• Biophysics
• Biochemistry
• Cell Biology

Background:

• Phase separation of intrinsically disordered proteins (IDPs) is crucial for forming membraneless organelles and regulating cellular biochemical processes.
• Biomolecular condensates, formed via phase separation, are essential cellular structures.

Purpose of the Study:

• To investigate the phase behavior of intrinsically disordered proteins using a coarse-grained model.
• To explore how variations in hydrophobic content and distribution affect protein phase separation.

Main Methods:

• Simulation of a coarse-grained model for intrinsically disordered proteins.
• Analysis of sequences with varying hydrophobic fractions and distributions.
• Characterization of liquid-liquid phase separation, critical points, and aggregate formation.

Main Results:

• Sequences with higher hydrophobicity exhibited conventional liquid-liquid phase separation.
• Lower hydrophobicity sequences showed re-entrant phase behavior and aggregate formation with complex geometries.
• Terminal bead composition influenced critical point location and interfacial tension.

Conclusions:

• Protein sequence order significantly impacts phase behavior, leading to diverse structures beyond simple liquid phases.
• These findings highlight the biological relevance of subtle sequence modifications in regulating protein phase separation and condensate formation.