The interior of cells contains numerous components that need to be carefully organized to fulfill a wide range of functions. The most widespread intracellular compartments completely lack membranes. Instead of membranes, these compartments (biomolecular condensates) are segregated via liquidliquid phase separation, analogous to how oil drops separate in water. Computer simulations have surfaced as powerful tools for providing us with the missing close-up views to understand the modulation of biomolecular phase behavior.
In this talk, I will describe the use of simulations to elucidate the molecular grammar underlying phase separation and account for salt-mediated reentrant phase transitions observed experimentally. I will explain how our simulations reveal distinctly different molecular driving forces stabilizing condensates in the low- and high-salt regime. I will also discuss current efforts at developing computer models that can predict biomolecular phase boundaries with quantitative accuracy. Finally, I will outline how we can advance the state-of-the-art to not only understand phase separation at the molecular level but to tune and control it on demand.