Computational resources for identifying and describing proteins driving liquid–liquid phase separation

Abstract

Abstract One of the most intriguing fields emerging in current molecular biology is the study of membraneless organelles formed via liquid–liquid phase separation (LLPS). These organelles perform crucial functions in cell regulation and signalling, and recent years have also brought about the understanding of the molecular mechanism of their formation. The LLPS field is continuously developing and optimizing dedicated in vitro and in vivo methods to identify and characterize these non-stoichiometric molecular condensates and the proteins able to drive or contribute to LLPS. Building on these observations, several computational tools and resources have emerged in parallel to serve as platforms for the collection, annotation and prediction of membraneless organelle-linked proteins. In this survey, we showcase recent advancements in LLPS bioinformatics, focusing on (i) available databases and ontologies that are necessary to describe the studied phenomena and the experimental results in an unambiguous way and (ii) prediction methods to assess the potential LLPS involvement of proteins. Through hands-on application of these resources on example proteins and representative datasets, we give a practical guide to show how they can be used in conjunction to provide in silico information on LLPS.