TY - JOUR
T1 - Phase separation vs aggregation behavior for model disordered proteins
AU - Rana, Ushnish
AU - Brangwynne, Clifford P.
AU - Panagiotopoulos, Athanassios Z.
N1 - Funding Information:
This research study was primarily supported by the Princeton Center for Complex Materials (PCCM), a U.S. National Science Foundation Materials Research Science and Engineering Center (Grant Nos. DMR-1420541 and DMR-2011750). The authors thank Antonia Statt for valuable comments and discussions. The authors thank the anonymous reviewer who suggested a higher value of charge for the tail residues. Simulations were performed using computational resources provided by the Princeton Institute for Computational Science and Engineering (PICSciE) and the Office of Information Technology’s High Performance Computing Center and Visualization Laboratory at Princeton University.
Publisher Copyright:
© 2021 Author(s).
PY - 2021/9/28
Y1 - 2021/9/28
N2 - Liquid-liquid phase separation (LLPS) is widely utilized by the cell to organize and regulate various biochemical processes. Although the LLPS of proteins is known to occur in a sequence-dependent manner, it is unclear how sequence properties dictate the nature of the phase transition and thereby influence condensed phase morphology. In this work, we have utilized grand canonical Monte Carlo simulations for a simple coarse-grained model of disordered proteins to systematically investigate how sequence distribution, sticker fraction, and chain length impact the formation of finite-size aggregates, which can preempt macroscopic phase separation for some sequences. We demonstrate that a normalized sequence charge decoration (SCD) parameter establishes a “soft” predictive criterion for distinguishing when a model protein undergoes macroscopic phase separation vs finite aggregation. Additionally, we find that this order parameter is strongly correlated with the critical density for phase separation, highlighting an unambiguous connection between sequence distribution and condensed phase density. Results obtained from an analysis of the order parameter reveal that at sufficiently long chain lengths, the vast majority of sequences are likely to phase separate. Our results suggest that classical LLPS should be the primary phase transition for disordered proteins when short-ranged attractive interactions dominate and suggest a possible reason behind recent findings of widespread phase separation throughout living cells.
AB - Liquid-liquid phase separation (LLPS) is widely utilized by the cell to organize and regulate various biochemical processes. Although the LLPS of proteins is known to occur in a sequence-dependent manner, it is unclear how sequence properties dictate the nature of the phase transition and thereby influence condensed phase morphology. In this work, we have utilized grand canonical Monte Carlo simulations for a simple coarse-grained model of disordered proteins to systematically investigate how sequence distribution, sticker fraction, and chain length impact the formation of finite-size aggregates, which can preempt macroscopic phase separation for some sequences. We demonstrate that a normalized sequence charge decoration (SCD) parameter establishes a “soft” predictive criterion for distinguishing when a model protein undergoes macroscopic phase separation vs finite aggregation. Additionally, we find that this order parameter is strongly correlated with the critical density for phase separation, highlighting an unambiguous connection between sequence distribution and condensed phase density. Results obtained from an analysis of the order parameter reveal that at sufficiently long chain lengths, the vast majority of sequences are likely to phase separate. Our results suggest that classical LLPS should be the primary phase transition for disordered proteins when short-ranged attractive interactions dominate and suggest a possible reason behind recent findings of widespread phase separation throughout living cells.
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U2 - 10.1063/5.0060046
DO - 10.1063/5.0060046
M3 - Article
C2 - 34598580
AN - SCOPUS:85115918170
SN - 0021-9606
VL - 155
JO - Journal of Chemical Physics
JF - Journal of Chemical Physics
IS - 12
M1 - 125101
ER -