First-generation predictors of biological protein phase separation

Biological condensates, including membraneless organelles, can consist of hundreds of proteins, and it is important to identify which proteins are driving condensation and which proteins have evolved to regulate protein compartmentalization by liquid-liquid phase separation. Predictors that have been used for this purpose have emerged from a variety of perspectives and have diverse designs, sequence dependencies, and physical bases. Here, we describe, compare, and contrast a range of first-generation phase-separation predictors currently available to demonstrate their overlapping and unique predictions and to highlight the need for second-generation predictors that would more comprehensively incorporate the multiple features associated with phase separation.