Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
Various physics- and data-driven sequence-dependent protein coarse-grained models have been developed to study biomolecular phase separation 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. We provide a comprehensive set of benchmarks for Mpipi and seven other residue-level coarse-grained models against experimental radii of gyration and quantitative in-vitro phase diagrams; Mpipi predictions agree well with experiment on both fronts. Moreover, it can account for protein–RNA interactions, correctly predicts the multiphase behaviour of a charge-matched poly-arginine/poly-lysine/RNA system, and recapitulates experimental LLPS trends for sequence mutations on FUS, DDX4 and LAF-1 proteins.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
2662-8457
Volume Title
Publisher
Publisher DOI
Rights
Sponsorship
EPSRC (EP/N509620/1)
Engineering and Physical Sciences Research Council (EP/P020259/1)
EPSRC (EP/T517847/1)
Engineering and Physical Sciences Research Council (EP/N509620/1)