Role of Strong Localized vs Weak Distributed Interactions in Disordered Protein Phase Separation

Area of Science:

• Biophysics
• Computational Biology
• Polymer Physics

Background:

• Intrinsically disordered proteins (IDPs) exhibit complex behaviors governed by interaction strength and localization.
• These parameters critically influence both single-chain properties and condensed-state behavior of IDPs.

Purpose of the Study:

• To investigate the relationship between interaction localization and phase behavior in intrinsically disordered proteins (IDPs).
• To compare two distinct coarse-grained models (HP and HP+ models) representing IDPs with different interaction types.

Main Methods:

• Utilized coarse-grained heteropolymer models with varying fractions of hydrophobic (H) and polar (P) monomers (X_P).
• Employed two models: HP (localized H-H attractions) and HP+ (distributed H-H and H-P attractions).
• Tuned attraction strengths to match single-chain radius of gyration for model and sequence comparison.

Main Results:

• Single-chain properties (conformation, energy, dynamics) were largely similar across models and sequences after tuning, except for HP at high X_P.
• Phase behavior diverged significantly, with limited phase separation observed in both models up to a model-dependent X_P.
• Self-assembly into finite-sized clusters, rather than bulk phase separation, was observed due to limited attractive sites.

Conclusions:

• Single-chain similarity does not guarantee similar phase-separation propensity in IDP models.
• Distributed interaction models (HP+) favor liquid-like condensate formation over a broader range of sequences compared to localized models (HP).
• The nature of interactions (localized vs. distributed) is a key determinant of condensate formation in IDPs.