Physics-driven coarse-grained models for understanding and engineering biomolecular condensates

Biomolecular condensates are membraneless compartments within living cells, composed of proteins and nucleic acids. They play essential roles in cellular functions and dysfunctions and offer a promising platform for engineering novel cellular functions. However, several questions remain unanswered about the mechanisms by which the material properties of condensates are encoded and how their functions emerge. To address these challenges, experimental approaches have been developed to perturb and measure condensates. Molecular simulations have become an invaluable complement to these efforts, providing detailed, close-up views of condensates. I will discuss how we develop coarse-grained models that balance accuracy and computational efficiency and leverage these approaches to recapitulate condensates in silico at submolecular resolution. Collectively, our framework connects condensate composition to their emergent behaviors, uncovering design principles that can be harnessed to engineer condensates.