Journal Article

catGRANULE 2.0: accurate predictions of liquid-liquid phase separating proteins at single amino acid resolution

Fiorentino, Jonathan, Cotrufo, Tiziana, Miltiadis-Vrachnos, Dimitrios, Sanchez de Groot, Natalia, Armaos, Alexandros, Bini, Giorgio, Monti, Michele, Tartaglia, Gian Gaetano

2025

Overview

Liquid-liquid phase separation (LLPS) enables the formation of membraneless organelles, essential for cellular organization and implicated in diseases. We introduce catGRANULE 2.0 ROBOT, an algorithm integrating physicochemical properties and AlphaFold-derived structural features to predict LLPS at single-amino-acid resolution. The method achieves high performance and reliably evaluates mutation effects on LLPS propensity, providing detailed predictions of how specific mutations enhance or inhibit phase separation. Supported by experimental validations, including microscopy data, it predicts LLPS across diverse organisms and cellular compartments, offering valuable insights into LLPS mechanisms and mutational impacts. The tool is freely available at https://tools.tartaglialab.com/catgranule2 and https://doi.org/10.5281/zenodo.14205831 .

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Algorithms / Amino acids / Amino Acids - chemistry / Animal Genetics and Genomics / Bioinformatics / Biomedical and Life Sciences / Datasets / Enzymes / Evolutionary Biology / genome / Human Genetics / Life Sciences / Liquid-liquid phase separation / Machine learning / Microbial Genetics and Genomics / microscopy / Mutation / Mutations / Ontology / Organelles / Phase transitions / Physicochemical properties / Plant Genetics and Genomics / Protein features / Proteins / Proteins - chemistry / Proteins - genetics / Robots / separation / Software / Subcellular compartmentalisation / Subcellular compartmentalization