LASSI: A lattice model for simulating phase transitions of multivalent proteins

by Jeong-Mo Choi, Furqan Dar, Rohit V. Pappu

Many biomolecular condensates form via spontaneous phase transitions that are driven by multivalent proteins. These molecules are biological instantiations ofassociative polymers that conform to a so-calledstickers-and-spacers architecture. The stickers are protein-protein or protein-RNA interaction motifs and / or domains that can form reversible, non-covalent crosslinks with one another. Spacers are interspersed between stickers and their preferential interactions with solvent molecules determine the cooperativity of phase transitions. Here, we report the development of an open source computational engine known as LASSI (LAttice simulation engine for Sticker and Spacer Interactions) that enables the calculation of full phase diagrams for multicomponent systems comprising of coarse-grained representations of multivalent proteins. LASSI is designed to enable computationally efficient phenomenological modeling of spontaneous phase transitions of multicomponent mixtures comprising of multivalent proteins and RNA molecules. We demonstrate the application of LASSI using simulations of linear and branched multivalent proteins. We show that dense phases are best described as droplet-spanning networks that are characterized by reversible physical crosslinks among multivalent proteins. We connect recent observations regarding correlations between apparent stoichiometry and dwell times of condensates to being proxies for the internal struc...

Source: PLoS Computational Biology - October 20, 2019 Category: Biology Authors: Jeong-Mo Choi Source Type: research