Liquid-liquid phase coexistence and separation in biological systems: focus on the DDX3X protein

• Grant number: 24/18313-0
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: June 26, 2025
• End date: July 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Jose Rafael Bordin
• Grantee: Maria Emily Nayla Gomes da Silva
• Host Institution: INST FISICA MATEMATICA/UFPEL

Abstract

Liquid-liquid phase separation (LLPS) plays a crucial role in organizing macromolecules into membraneless compartments, such as biomolecular condensates, which regulate essential processes, including transcription and RNA metabolism. Dysregulation of this process is associated with various diseases, including neurodegeneration and cancer. The DDX3X protein, a DEAD-box family helicase, is a key protein involved in LLPS and is associated with pathological mutations that can lead to protein aggregation. This project aims to explore, through molecular dynamics simulations, how mutations in DDX3X, particularly L556S, affect phase separation and contribute to protein aggregate formation, providing insights into potential therapeutic approaches. A coarse-grained model will be employed to reduce computational complexity, allowing for large system simulations, and the LAMMPS software will be used for the simulations.