Biomolecular modelling of the intrinsically disordered proteins in liquid-liquid phase separation

• Main Author: Hu, Zixin
• Other Authors: Lu Lanyuan
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2025
• Subjects: Chemistry; Computer and Information Science; Medicine, Health and Life Sciences; Other; Biomolecular modelling; Coarse-grained model; Intrinsically disordered proteins/regions; Liquid-liquid phase separation; Molecular dynamics simulation
• Online Access: https://hdl.handle.net/10356/182665
• Institution: Nanyang Technological University

Liquid-liquid phase separation (LLPS) is of significant biological importance and is widely reported in many biological systems. Intrinsically disordered proteins or regions (IDP/Rs) are a class of proteins or regions that lack well-folded structures and are thought to be a major driving force of LLPS. This thesis studied the function of IDP/Rs in biomolecular LLPS systems with computational tools, mainly molecular simulation. It contains three parts. First, it studied the role of IDRs in fine-tuning the oligomerization of Coronin, which is important in regulating actin polymerization. Second, it developed a new coarse-grained (CG) model with refined bonded potentials to improve the backbone conformation of IDP/Rs. Third, it explored the multivalency of IDPs in a customized LLPS database to have a deeper insight into LLPS propensity. Collectively, this thesis provided a more accurate computational tool to study IDP/Rs and contributed to understanding the functions of IDP/Rs and the nature of LLPS.