A coarse-grained model of disordered RNA for simulations of biomolecular condensates

Abstract

Protein-RNA condensates are involved in a range of cellular activities. Coarse-grained molecular models of intrinsically disordered proteins have been developed to shed light on and predict single-chain properties and phase separation. An RNA model compatible with such models for disordered proteins would enable the study of complex biomolecular mixtures involving RNA. Here, we present a sequence-independent coarse-grained, two-bead-per-nucleotide model of disordered, flexible RNA based on a hydropathy scale. We parameterize the model, which we term CALVADOS-RNA, using a combination of bottom-up and top-down approaches to reproduce local RNA geometry and intramolecular interactions based on atomistic simulations and in vitro experiments. The model semi-quantitatively captures several aspects of RNA-RNA and RNA-protein interactions. We examined RNA-RNA interactions by comparing calculated and experimental virial coefficients, and non-specific RNA-protein interaction by studying reentrant phase behavior of protein-RNA mixtures. We demonstrate the utility of the model by simulating the formation of mixed condensates consisting of the disordered region of MED1 and RNA chains, and the selective partitioning of disordered regions from transcription factors into these, and compare the results to experiments. Despite the simplicity of our model we show that it captures several key aspects of protein-RNA interactions and may therefore be used as a baseline model to study several aspects of the biophysics and biology of protein-RNA condensates.