Probing molecular and biophysical mechanisms of RNA and protein phase transitions with simulations and theory

Biomolecular condensates play crucial roles in cellular organisation, regulating diverse biological functions as well as contributing to disease pathologies when phase separation is dysregulated. Computer simulations and theoretical approaches have emerged as powerful tools to probe the molecular mechanisms governing phase transitions in these systems. This review highlights recent advancements in computational methods, focusing on coarse-grained and all-atom molecular dynamics simulations, to elucidate the driving forces underlying protein and RNA condensate formation and how their stability and material properties can be regulated and tuned. Additionally, we address new strategies for designing synthetic condensates with tunable properties and leveraging predictive models to guide experimental studies. The integration of molecular simulations, with data-driven approaches and theory, has expanded our understanding of biomolecular condensates, offering novel insights into both fundamental biology and physics, as well as potential practical applications.