Subcompartmentalization of polyampholyte species in organelle-like condensates is promoted by charge-pattern mismatch and strong excluded-volume interaction

Numerical Techniques for Applications of Analytical Theories to Sequence-Dependent Phase Separations of Intrinsically Disordered Proteins

“…This conclusion is in line with the aforementioned RPA prediction with regard to sequence charge pattern mismatch because a strong excluded volume was tacitly enforced in that prior formulation by an incompressibility constraint [24]. The finding underscores the sensitivity of FTS predictions to excluded-volume assumptions, urging caution in choosing and interpreting FTS parameters for excluded volume [25]. Insofar as electrostatic effects in polyampholyte LLPS are concerned, recent studies using FTS, RPA, and coarse-grained explicit-chain molecular dynamics of polyampholytes with a simplified explicit model of polar solvent suggest that a reduced relative permittivity contributed by the solvent in the condensed phase probably leads only to a small to moderate enhancement of LLPS propensity compared to that predicted by an implicit-solvent model that assigns a uniform relative permittivity corresponding to that of the bulk solvent throughout the entire system volume [34,35].…”

“…FTS has been applied to compute correlation functions for systems with two IDP species. The results indicate that sequence charge-pattern mismatch and a strong generic excluded volume repulsion are both necessary for two polyampholytic IDP species to demix, i.e., to subcompartmentalize, in the condensed phase [25]. This conclusion is in line with the aforementioned RPA prediction with regard to sequence charge pattern mismatch because a strong excluded volume was tacitly enforced in that prior formulation by an incompressibility constraint [24].…”

“…An application of RPA to the LLPS of systems with two IDP species first indicated that their populations in the condensed phase are miscible when the sequence charge patterns [22,23] of the two IDP species are similar, but they tend to demix into subcompartments when their sequence charge patterns are significantly different [24]. The robustness of this prediction has since been buttressed by explicit-chain coarse-grained molecular dynamics as well as field-theoretic simulations [25]. This finding highlights a stochastic, "fuzzy" type of molecular recognition that may contribute to subcompartmentalization of some biomolecular condensates [24] such as the nucleolus.…”

RNA chain length and stoichiometry govern surface tension and stability of protein-RNA condensates

“…Theoretical models ( Choi et al., 2020a ; Ruff et al., 2018 ; Zeng et al., 2020 ; Pappu, 2020 ; Lin et al., 2020 ; Huihui and Ghosh, 2020 ), molecular simulations ( Shea et al., 2021 ; Regy et al., 2020 ; Dignon et al., 2020 ; Ruff et al., 2018 ; Choi et al., 2019 ), and field theoretical simulations ( Pal et al., 2021 ; McCarty et al., 2019 ; Laghmach and Potoyan, 2020 ) of biomolecular phase transitions have emerged to play an increasingly important role alongside experiments in shedding light on the sequence-encoded driving forces as well as biophysical and material properties of condensates. One of the emerging theoretical frameworks from these studies is the stickers-and-spacers framework ( Choi et al., 2020a , 2020b ; Brangwynne et al., 2015 ; Chong and Mir, 2021 ) inspired from the field of associative polymers.…”

Current Understanding of Molecular Phase Separation in Chromosomes

“…To further reduce the computational cost, the polymer system can be depicted by functional integrals over fluctuating fields; this is referred to as the field-theoretic approach [139]. This approach has recently been utilized to study biomolecular phase separation, especially when electrostatic interactions are dominant [140][141][142].…”