Temperature-Dependent Coarse-Grained Model for Simulations of Intrinsically Disordered Protein LCST and UCST...

Area of Science:

• Biophysics
• Computational Biology
• Protein Science

Background:

• Intrinsically disordered proteins (IDPs) exhibit liquid-liquid phase separation (LLPS) influenced by environmental factors like temperature.
• Temperature-dependent LLPS occurs as either lower critical solution temperature (LCST) or upper critical solution temperature (UCST) phenomena.
• Coarse-grained (CG) models are valuable for studying IDP LLPS, but models capturing both LCST and UCST behaviors are limited.

Purpose of the Study:

• To develop a novel temperature-dependent (TD) coarse-grained (CG) model for simulating intrinsically disordered proteins (IDPs).
• To enable simulations of both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) behaviors in IDPs.
• To provide a computational tool for investigating the physical and chemical drivers of IDP phase separation.

Main Methods:

• Developed a TD CG model based on the MARTINI 3 force field.
• Modified Lennard-Jones potentials using a TD rescaling factor for interactions between solute beads and water.
• Parametrized the model using temperature-dependent potentials of mean force (PMF) from all-atom (AA) simulations.

Main Results:

• The TD CG model successfully reproduced experimentally observed LLPS for both LCST and UCST low-complexity sequences.
• Estimated phase transition temperatures using the model showed good agreement with experimental measurements.
• Demonstrated the model's capability to simulate temperature-sensitive IDP phase behavior.

Conclusions:

• The novel TD CG model accurately captures temperature-dependent LLPS (LCST and UCST) of IDPs.
• This model advances the simulation capabilities for studying phase transitions in IDPs.
• The developed model offers a valuable tool for predicting and understanding IDP behavior under varying conditions.