Prediction and characterization of liquid-liquid phase separation of minimalistic peptides

Tang, Yuanyan; Bera, Santu; Yao, Yifei; Zeng, Jiyuan; Lao, Zenghui; Dong, Xiaowei; Gazit, Ehud; Wei, Guanghong

doi:10.1016/j.xcrp.2021.100579

Cited by 48 publications

(73 citation statements)

References 77 publications

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“…10,12,13 The formation of aggregates as opposed to liquid-like condensates in the case of patchy sequences with clusters of stickers 12 may be understood as being closer to the results from our simulations of Tyr-only boxes, which result in the formation of condensates with greater degree dynamical arrest, as monitored by both diffusion constants and intramolecular dynamics. Our work also confirms in full atomistic detail recent results by Tang et al, 25 who explored dipeptide solutions in simulations using the intermediate-resolution MARTINI model. 48 Further evidence for the generality of LLPS is accumulating in the experimental front in a broad range of lengthscales, from short peptides 49,50 to globular proteins.…”

Section: Discussionsupporting

confidence: 90%

“…LSPS). Our work also confirms in full atomistic detail recent results by Tang et al, 33 who explored dipeptide solutions in simulations using the intermediate-resolution MARTINI model. 36 Further evidence for the generality of LLPS is accumulating in the experimental front in a broad range of length-scales, from short peptides 37,38 to globular proteins.…”

supporting

confidence: 90%

“…S3). This type of intermediate behaviour for the Gly/Ser/Tyr mixture is also observed for the maximum cluster size, which has also been shown to be a robust descriptor of the degree of clustering 25 (Fig. 2A).…”

Section: Clustering Degree and Aggregation Propensity As Metrics Of C...supporting

confidence: 62%

“…Two useful metrics that summarize the information from these simulations are the "aggregation propensity", defined as the ratio between the initial and instantaneous solvent accessible surface areas, 42 and the "clustering degree", which we obtain normalizing the maximum cluster size by the total number of residues in the box. 25 In the projection of our datasets on these axes (Fig. 2B), the Gly/Ser/Tyr system stands out as having intermediate values of the aggregation propensity and clustering degree between the systems that do not phase separate (Gly, Ser and Gly/Ser mixture)…”

Section: Clustering Degree and Aggregation Propensity As Metrics Of C...mentioning

confidence: 91%

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Phase separation in amino acid mixtures is governed by composition

Sancho

2022

Preprint

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Liquid-liquid phase separation (LLPS) has recently come to immense prominence as it is central to the formation of membraneless organelles, leading to a new paradigm of cellular organization. This type of phase transition is mediated by molecular interactions between biomolecules, including nucleic acids and both ordered and disordered proteins. In the latter case, the separation between protein-dense and dilute phases is often interpreted using models adapted from polymer theory. Specifically, the "stickers and spacers" model proposes that LLPS originates from the interplay between two classes of residues and that the main determinants for phase separation are multivalency and sequence patterning. The duality of roles of stickers (aromatics like Phe and Tyr) and spacers (Gly and polar residues) may apply more broadly in protein-like mixtures, and the presence of these two types of components alone may suffice for LLPS to take place. In order to explore this hypothesis, we use atomistic molecular dynamics simulations of capped amino-acid residues as a minimal model system. We study the behaviour of pure amino acids in water for three types of residues that are thought to play critical roles in LLPS, corresponding to the spacer and sticker categories, and their multicomponent mixtures. In agreement with previous observations, we find that the spacer type amino acids fail to phase-separate on their own, while the sticker is prone to aggregation. However, ternary amino acid mixtures involving both types of amino acids phase-separate into two phases that retain intermediate degrees of compaction and considerable fluidity. Our results suggest that LLPS is an emergent property of amino acid mixtures determined by composition.

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Section: Discussionsupporting

confidence: 90%

supporting

confidence: 90%

Section: Clustering Degree and Aggregation Propensity As Metrics Of C...supporting

confidence: 62%

Section: Clustering Degree and Aggregation Propensity As Metrics Of C...mentioning

confidence: 91%

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Phase separation in amino acid mixtures is governed by composition

Sancho

2022

Preprint

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“…This classical slab method has now been applied to a variety of coarse-grained models of biomolecular condensates, from spherical particles and homopolymers (as crude models of structured proteins and IDPs) 9–10 to residue-level models of IDPs 11–13 to multi-bead-per-residue models of dipeptides. 14 An exciting recent development is the migration of this method to simulations of all-atom models of IDPs in explicit solvent, by first carrying out full simulations at the coarse-grained level and then mapping to atomistic systems. 15–16 Still, the mapping is not a trivial task and, after mapping, simulations at the all-atom level may fail to allow exchange of protein molecules between the phases, let alone reaching phase equilibrium.…”

Section: Introductionmentioning

confidence: 99%

SpiDec: Computing Binodals and Interfacial Tension of Biomolecular Condensates From Simulations of Spinodal Decomposition

Mazarakos

Prasad

Zhou

2022

Preprint

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Phase separation of intrinsically disordered proteins (IDPs) is a phenomenon associated with many essential cellular processes, but a robust method to compute the binodal from molecular dynamics simulations of IDPs modeled at the all-atom level in explicit solvent is still elusive, due to the difficulty in preparing a suitable initial dense configuration and in achieving phase equilibration. Here we present SpiDec as such a method, based on spontaneous phase separation via spinodal decomposition that produces a dense slab when the system is initiated at a homogeneous, low density. After illustrating the method on four model systems, we apply SpiDec to a tetrapeptide modeled at the all-atom level and solvated in TIP3P water. The concentrations in the dense and dilute phases agree qualitatively with experimental results and point to binodals as a sensitive property for force-field parameterization. SpiDec may prove useful for the accurate determination of the phase equilibrium of IDPs.

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Cell‐Like Synthetic Supramolecular Soft Materials Realized in Multicomponent, Non‐/Out‐of‐Equilibrium Dynamic Systems

Kubota,

Hamachi

2023

Advanced Science

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Living cells are complex, nonequilibrium supramolecular systems capable of independently and/or cooperatively integrating multiple bio‐supramolecules to execute intricate physiological functions that cannot be accomplished by individual biomolecules. These biological design strategies offer valuable insights for the development of synthetic supramolecular systems with spatially controlled hierarchical structures, which, importantly, exhibit cell‐like responses and functions. The next grand challenge in supramolecular chemistry is to control the organization of multiple types of supramolecules in a single system, thus integrating the functions of these supramolecules in an orthogonal and/or cooperative manner. In this perspective, the recent progress in constructing multicomponent supramolecular soft materials through the hybridization of supramolecules, such as self‐assembled nanofibers/gels and coacervates, with other functional molecules, including polymer gels and enzymes is highlighted. Moreover, results show that these materials exhibit bioinspired responses to stimuli, such as bidirectional rheological responses of supramolecular double‐network hydrogels, temporal stimulus pattern‐dependent responses of synthetic coacervates, and 3D hydrogel patterning in response to reaction–diffusion processes are presented. Autonomous active soft materials with cell‐like responses and spatially controlled structures hold promise for diverse applications, including soft robotics with directional motion, point‐of‐care disease diagnosis, and tissue regeneration.

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Prediction and characterization of liquid-liquid phase separation of minimalistic peptides

Cited by 48 publications

References 77 publications

Phase separation in amino acid mixtures is governed by composition

Phase separation in amino acid mixtures is governed by composition

SpiDec: Computing Binodals and Interfacial Tension of Biomolecular Condensates From Simulations of Spinodal Decomposition

Cell‐Like Synthetic Supramolecular Soft Materials Realized in Multicomponent, Non‐/Out‐of‐Equilibrium Dynamic Systems

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