Machine learning

Chemistry

Materials science

Sequence (biology)

Intrinsically disordered proteins

Chemical physics

Biochemistry

Physics

Quantum mechanics

Computer science

Statistical physics

Separation (statistics)

Phase (matter)

Proceedings of the National Academy of Sciences

Significance Membraneless organelles are assemblies of highly concentrated biomolecules that form through liquid–liquid phase separation. These assemblies are often enriched in intrinsically disordered proteins (IDPs), which play an important role in driving phase separation. Understanding the sequence-to-phase behavior relationship of these disordered proteins is important for understanding the biochemistry of membraneless organelles, as well as for designing synthetic organelles and biomaterials. In this work, we explore a model protein, the disordered N-terminal domain of LAF-1, and highlight how three key features of the sequence control the protein’s propensity to phase-separate. Combining state-of-the-art simulations with experiments, we find that phase behavior of this model IDP is dictated by the presence of a short conserved domain, charge patterning, and arginine–tyrosine interactions.

Identifying sequence perturbations to an intrinsically disordered protein that determine its phase-separation behavior