Department of Chemistry - PhD Student Seminar - Liquid-Liquid Phase Separation  in Bio-system: Modeling and Simulation

Student: Mr. Wentao XU

Department: Department of Chemistry, HKUST

Supervisor(s): Professor Haibin SU

Abstract

This presentation systematically explores the phenomenon of liquid-liquid phase separation (LLPS) in biological systems, focusing on computational modeling and simulation analysis methods for this thermodynamic process. First, it outlines the biological background of LLPS, highlighting that it is primarily driven by transient multivalent interactions between intrinsically disordered regions (IDRs), and details the critical role of the "Scaffold and Client" model in physiological processes such as gene transcription and immune responses. In terms of computational modeling, the presentation focuses on coarse-grained models, delving into how to accurately describe the electrostatic shielding and hydrophobic interactions of IDRs by incorporating the Debye-Hückel theory and modified Lennard-Jones potentials (e.g., Ashbaugh-Hatch potential). Finally, using specific case studies including phase diagrams, critical scaling laws, and the comparison between the SARS-CoV-2 nucleocapsid protein (NP) and G3BP1, it demonstrates how molecular dynamics simulations can quantitatively analyze the regulatory mechanisms of factors like RNA concentration, temperature (e.g., LCST/UCST behavior), and salt concentration on phase behavior. Overall, the presentation elucidates that LLPS is a highly tunable thermodynamic process, and that coarse-grained modeling combined with phase diagram analysis provides a powerful tool for bridging the sequence characteristics of biomacromolecules with their macroscopic phase behavior.