Charge Arrangement Determines the Sensitivity of Aggregation Patterns between Peptide-Chains to the Surrounding Ionic...

Area of Science:

• Biochemistry
• Biophysics
• Molecular Biology

Background:

• Liquid-liquid phase separation (LLPS) is crucial for cellular organization, driven by multivalent, low-affinity interactions.
• Intrinsically disordered proteins (IDPs) with charged residues are key players in LLPS, but their salt-dependent behavior is not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms governing the phase separation of charged intrinsically disordered proteins (IDPs) in varying ionic environments.
• To elucidate the role of specific cations (Na+, Mg2+) in modulating the aggregation patterns and electrostatic interactions of oppositely charged peptides.

Main Methods:

• Computational modeling and simulation of peptide chains with extreme charge arrangements.
• Analysis of molecular interactions and aggregation patterns across diverse salt concentrations and ionic compositions.

Main Results:

• Non-uniform charge distribution in peptides leads to increased sensitivity to cationic environments.
• Na+ ions promote aggregation of aspartate (ASP) residues more than Mg2+ ions.
• Increasing salt concentration shifts interactions from charge-opposite to charge-bridged networks, with saturation observed.

Conclusions:

• Electrostatic interactions and ion-specific effects are critical determinants of LLPS in charged IDPs.
• Understanding these atomic-level electrostatic factors can guide the design of targeted LLPS applications.