Using a sequence-specific coarse-grained model for studying protein liquid–liquid phase separation

The formation of membraneless organelles (MLOs) via liquid–liquid phase separation (LLPS) of biomolecules is a topic that has garnered significant attention in the scientific community recently. Experimental studies have revealed that intrinsically disordered proteins (IDPs) may play a major role in driving the formation of these droplets via LLPS by forming multivalent interactions between amino acids. To quantify these interactions is an arduous task as it is difficult to investigate these interactions at the amino acid level using currently available experimental tools. It becomes necessary to complement experimental studies using appropriate computational methods such as coarse-grained models of IDPs that can allow one to simulate biomolecular LLPS using general-purpose hardware. Here, we summarize our coarse-grained modeling framework that uses a single bead per amino acid resolution and the co-existence sampling technique to study sequence-specific protein phase separation using molecular dynamics simulations. We further discuss the caveats and technicalities, which one must consider while using this method to obtain thermodynamic phase diagrams. To ease the learning curve, we provide our implementations of the coarse-grained potentials in the HOOMD-Blue simulation package and associated python scripts to run such simulations.