Simulation Informed Thermodynamic Model for Polyampholyte Self-Coacervation with Heterogeneous Charge Distribution

Livng cells rely on phase separation to achieve many of its critical functions such as organelle formation and signaling and regulatory complexation. Intrinsically disordered proteins (IDPs) often play a role in intracellular liquid-liquid phase separation. IDPs are frequently ampholytic and they can be driven to phase separation through electrostatic interactions. The solution behavior and properties are encoded in the peptide sequence of the proteins, particularly the distribution of the charged residues. Previous work from the authors introduced a Transfer Matrix model for charge-driven polyampholyte phase separation, which resolved the impact of charge sequence on phase separation. This model was limited to looking at homogenous sequences made up of repeating blocks of charge patterns. In this work we present a coarse-grained simulation model to resolve phase separation in polyampholytes with any arbitrary charge sequence. Of particular interest is characterizing the inhomogeneity of the sequence and quantifying the impact on solution behavior.