Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy

Abstract

In recent years, various physics- and data-driven sequence-dependent protein coarse-grained models have been developed to study biomolecular liquid—liquid phase separation (LLPS) and elucidate the dominant physicochemical driving forces. Here, we present Mpipi, a multiscale coarse-grained model that describes almost quantitatively the change in protein critical temperatures as a function of amino-acid sequence. The model is parameterised from both atomistic simulations and bioinformatics data and accounts for the dominant role of π–π and hybrid cation–π/π–π interactions and the much stronger attractive contacts established by arginines than lysines.