Proteins undergo liquid-liquid phase separation (LLPS), resulting in dynamic biomolecular condensates, such as stress granules and nucleoli. Alterations in the physical characteristics of these condensates are recognized as drivers of pathological transitions linked to aging, cancer, and neurodegenerative disorders. A hallmark of such diseases is the phase transitions of condensates from liquid or gel-like assemblies into solid-like states. The material properties of condensates are influenced by the presence of both folded and unfolded domains within proteins. In this study, we applied coarse-grained, amino acid resolution simulations to characterize how folded domains modulate condensate physical properties. By optimizing the simulation model based on experimental data, we characterize how globular protein sequences modulate the material properties of condensates. These findings provide molecular-level insights into the structure and dynamics of condensates and offer potential implications for understanding LLPS-associated diseases and protein complex formation.
Ayoung Jeong (Sun,) studied this question.