Atomistic Simulations of Biomolecular Condensates

Biomolecular condensates formed through liquid-liquid phase separation (LLPS) play essential roles in various cellular processes. Understanding the molecular interactions, conformational dynamics, and solvent effects within these condensates is important for elucidating their functionality. However, studying these properties remains challenging. Atomistic condensedphase simulations provide a powerful computational approach to complement experimental studies by offering high-resolution insights into these complex systems. In this chapter, we present a workflow for generating atomistic structures of biomolecular condensates from coarse-grained (CG) simulations. By performing coexistence CG simulations, we obtain equilibrated condensedphase structures, which are then backmapped to all-atom (AA) models. We outline the technical considerations and common challenges in obtaining stable AA configurations and provide strategies for generating robust condensed-phase structures for molecular dynamics (MD) simulations. This approach enables the characterization of intermolecular interactions, solvent and ion partitioning, and conformational properties. We anticipate this chapter will serve as a valuable resource for researchers studying atomistic condensed phase simulations, providing a framework for investigating the molecular mechanisms underlying phase separation and further advancing our understanding of biomolecular organization and function.