Multi-scale molecular simulation of random peptide phase separation and its extended-to-compact structure transition...

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• Intrinsically disordered proteins (IDPs) are crucial for forming membraneless organelles via liquid-liquid phase separation (LLPS).
• Understanding the interplay of electrostatic and hydrophobic forces in IDP phase separation remains a key challenge.

Purpose of the Study:

• To investigate how electrostatic repulsion and hydrophobic interactions in peptides regulate the LLPS process.
• To establish a relationship between amino acid sequence and phase behavior in model peptide systems.

Main Methods:

• Utilized large-scale simulations employing both all-atom and coarse-grained multi-scale modeling.
• Focused on analyzing the phase separation behavior of random peptides composed of arginine (R) and isoleucine (I) using a coarse-grained model.

Main Results:

• Increased electrostatic repulsion resulted in more extended single-chain structures and a tendency towards low-density homogeneous phases.
• Enhanced hydrophobic interactions led to more compact single-chain structures, facilitating phase separation and increasing the critical temperature.

Conclusions:

• The study provides theoretical insights into the sequence-dependent phase behavior of IDPs.
• Findings offer crucial physical information for designing functional IDPs and understanding LLPS-associated diseases.