Model for disordered proteins with strongly sequence-dependent liquid phase behavior.

TitleModel for disordered proteins with strongly sequence-dependent liquid phase behavior.
Publication TypeJournal Article
Year of Publication2020
AuthorsStatt, A, Casademunt, H, Brangwynne, CP, Panagiotopoulos, AZ
JournalJ Chem Phys
Date Published2020 Feb 21
KeywordsHydrophobic and Hydrophilic Interactions, Intrinsically Disordered Proteins, Models, Molecular, Phase Transition

<p>Phase separation of intrinsically disordered proteins is important for the formation of membraneless organelles or biomolecular condensates, which play key roles in the regulation of biochemical processes within cells. In this work, we investigated the phase separation of different sequences of a coarse-grained model for intrinsically disordered proteins and discovered a surprisingly rich phase behavior. We studied both the fraction of total hydrophobic parts and the distribution of hydrophobic parts. Not surprisingly, sequences with larger hydrophobic fractions showed conventional liquid-liquid phase separation. The location of the critical point was systematically influenced by the terminal beads of the sequence due to changes in interfacial composition and tension. For sequences with lower hydrophobicity, we observed not only conventional liquid-liquid phase separation but also re-entrant phase behavior in which the liquid phase density decreases at lower temperatures. For some sequences, we observed the formation of open phases consisting of aggregates, rather than a normal liquid. These aggregates had overall lower densities than the conventional liquid phases and exhibited complex geometries with large interconnected string-like or membrane-like clusters. Our findings suggest that minor alterations in the ordering of residues may lead to large changes in the phase behavior of the protein, a fact of significant potential relevance for biology.</p>

Alternate JournalJ Chem Phys
PubMed ID32087632