Open AccessPhysics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy
Author(s) -
Jerelle A. Joseph,
Aleks Reinhardt,
Anne Aguirre,
Pin Yu Chew,
Kieran O. Russell,
Jorge R. Espinosa,
Adiran Garaizar,
Rosana Collepardo-Guevara
Publication year - 2021
Publication title -
nature computational science
Language(s) - English
Resource type - Journals
ISSN - 2662-8457
DOI - 10.1038/s43588-021-00155-3
Subject(s) - biological system , statistical physics , chemical physics , physics , molecular dynamics , chemistry , biophysics , computational chemistry , biology
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.