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Analytical Formulation and Field-Theoretic Simulation of Sequence-Specific Phase Separation of Protein-Like
Jonas Wessén1, Suman Das1, Tanmoy Pal1
1Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
The Journal of Physical Chemistry. B
|November 7, 2022
Summary
We developed a theory for sequence-dependent liquid-liquid phase separation (LLPS) in intrinsically disordered proteins (IDPs). This model incorporates both short-range and long-range interactions for accurate predictions of LLPS behavior.
Area of Science:
- Biophysics
- Computational Biology
- Protein Science
Background:
- Intrinsically disordered proteins (IDPs) undergo liquid-liquid phase separation (LLPS) to form biomolecular condensates.
- Understanding sequence-specific LLPS is crucial for deciphering cellular organization and function.
Purpose of the Study:
- To formulate a comprehensive theory for sequence-dependent LLPS of IDPs.
- To integrate short-range and long-range interactions into a unified theoretical framework.
Main Methods:
- Extended random phase approximation (RPA) and field-theoretic simulations (FTS) of heteropolymers.
- Modeled short-range interactions using Yukawa potentials and long-range electrostatics.
- Incorporated chain excluded volume via incompressibility constraints.
Main Results:
- Developed a mean-field approximation yielding an effective Flory-Huggins parameter (χ).
- RPA and mean-field approach capture composition and sequence-pattern effects on LLPS.
- FTS provides full sequence dependence for both interaction types.
Conclusions:
- The presented theory accurately predicts sequence-dependent LLPS in IDPs.
- Methodology validated against coarse-grained explicit-chain molecular dynamics simulations.
- Offers a powerful tool for studying IDP phase separation and condensate formation.
