Uncovering the thermodynamic principles of enzymatic regulation in biomolecular condensates with reactive simulations

Biomolecular condensates are dynamic cellular assemblies often regulated by energy-consuming processes such as post-translational modifications (PTMs). These reactions can act as molecular switches that control condensate assembly and dissolution, or sustain non-equilibrium steady states (NESS) that allow condensates to effectively perform their biological role. Nevertheless, the coupling between reaction dynamics and cellular spatial organization remains poorly understood at the molecular scale. Here, we introduce a minimal molecular model to explore regulation of condensate assembly and structure by energy-consuming enzymatic reactions, such as phosphorylation, under thermodynamic constraints. Our simulations reveal non-trivial trends in how the strength of enzymatic modification influences condensate stability, suggesting potential strategies for optimal control. We also find that chemical activity becomes spatially focused at the condensate interface, which emerges as a key reactive hub shaped by local molecular environments. These findings highlight the potential of thermodynamically consistent, particle-based simulations to uncover principles of active condensate regulation at molecular resolution.