Molecular mechanisms of small molecules that modulate the properties of biomolecular condensates

Biomolecular condensates are dynamic mesoscopic cellular assemblies stabilized by numerous weak, transient, and multivalent interactions between disordered proteins, folded proteins, and nucleic acids.  Biomolecular condensates are formed through liquid-liquid phase separation-like processes within cells, often driven by multivalent interactions of disordered proteins. Condensates are increasingly recognized as crucial regulators of cellular function and have been implicated in numerous human diseases.  Small molecules that alter the stability, composition or function of condensates show potential for ameliorating disease states resulting from condensate dysfunction.  Here, we apply all-atom molecular dynamics (MD) computer simulations to understand the mechanisms by which small molecules modulate the properties of biomolecular condensates.