Calculating Binodals and Interfacial Tension of Phase-Separated Condensates from Molecular Simulations with Finite-Size Corrections

Mazarakos, Konstantinos; Qin, Sanbo; Zhou, Huan‐Xiang

doi:10.1007/978-1-0716-2663-4_1

Cited by 5 publications

(11 citation statements)

References 38 publications

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“…The chemical potential 𝜇 is the free energy on a per-molecule basis. For a protein solution, the dependence of the chemical potential on protein concentration (𝜌) allows the determination of the binodal 4,27 . 𝜇 can be decomposed into…”

Section: Crystallinsmentioning

confidence: 99%

“…We then add the ideal part to the corrected 𝜇 #$ and perform an equal-area construction 24,27 (Fig. 3B) to the concentrations in the coexisting dilute and dense phases.…”

Section: Binodals Determined From Concentration Dependence Of Chemica...mentioning

confidence: 99%

“…A cutoff of 12 Å was imposed for calculating interactions between two atoms. For a given configuration 𝐗 of the protein solution and a given orientation 𝛀 of the test protein, the interaction energy 𝑈(𝐗, 𝛀, 𝐑) when placing the position 𝐑 of test protein at any of the 540 3 = 1.57464 ´ 10 8 points on a cubic grid was calculated using FMAP 24,27,29 . For each protein concentration, the calculation was repeated 2,000 ´ 500 = 10 6 times, combining 2,000 protein configurations with 500 orientations of the test protein.…”

Section: Fmapµ Calculationsmentioning

confidence: 99%

“…The details of polynomial fit and equal-area construction are described in Ref 27 . A web server implementing these steps is at https://zhougroup-uic.github.io/LLPS/.…”

Section: Fmapµ Calculationsmentioning

confidence: 99%

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Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence

Qin

Zhou

2023

Preprint

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Liquid-liquid phase separation of protein solutions has regained heightened attention for its biological importance and pathogenic relevance. Coarse-grained models are limited when explaining residue-level effects on phase equilibrium. Here we report phase diagrams for γ-crystallins using atomistic modeling. The calculations were made possible by combining our FMAP method for computing chemical potentials and Brownian dynamics simulations for configurational sampling of dense protein solutions, yielding the binodal and critic temperature (Tc). We obtain a higher Tcfor a known high-Tcγ-crystallin, γF, than for a low-Tcparalog, γB. The difference in Tcis corroborated by a gap in second virial coefficient. Decomposition of inter-protein interactions reveals one amino-acid substitution between γB and γF, from Ser to Trp at position 130, as the major contributor to the difference in Tc. This type of analysis enables us to link phase equilibrium to amino-acid sequence and to design mutations for altering phase equilibrium.

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Section: Crystallinsmentioning

confidence: 99%

“…We then add the ideal part to the corrected 𝜇 #$ and perform an equal-area construction 24,27 (Fig. 3B) to the concentrations in the coexisting dilute and dense phases.…”

Section: Binodals Determined From Concentration Dependence Of Chemica...mentioning

confidence: 99%

Section: Fmapµ Calculationsmentioning

confidence: 99%

“…The details of polynomial fit and equal-area construction are described in Ref 27 . A web server implementing these steps is at https://zhougroup-uic.github.io/LLPS/.…”

Section: Fmapµ Calculationsmentioning

confidence: 99%

See 2 more Smart Citations

Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence

Qin

Zhou

2023

Preprint

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“…Over the years, a variety of methods have been developed to compute the binodals of coarse-grained model systems (for a brief review and illustration, see Mazarakos et al, 2023 ). One of the earliest methods is based on preparing a dense slab at the center of an otherwise empty simulation box ( Rao and Levesque, 1976 ).…”

Section: Introductionmentioning

confidence: 99%

SpiDec: Computing binodals and interfacial tension of biomolecular condensates from simulations of spinodal decomposition

Mazarakos

Prasad²,

Zhou³

2022

Front. Mol. Biosci.

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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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Fundamental Aspects of Phase-Separated Biomolecular Condensates

Zhou,

Kota,

Qin

et al. 2024

Chem. Rev.

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Biomolecular condensates, formed through phase separation, are upending our understanding in much of molecular, cell, and developmental biology. There is an urgent need to elucidate the physicochemical foundations of the behaviors and properties of biomolecular condensates. Here we aim to fill this need by writing a comprehensive, critical, and accessible review on the fundamental aspects of phase-separated biomolecular condensates. We introduce the relevant theoretical background, present the theoretical basis for the computation and experimental measurement of condensate properties, and give mechanistic interpretations of condensate behaviors and properties in terms of interactions at the molecular and residue levels.

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Calculating Binodals and Interfacial Tension of Phase-Separated Condensates from Molecular Simulations with Finite-Size Corrections

Cited by 5 publications

References 38 publications

Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence

Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence

SpiDec: Computing binodals and interfacial tension of biomolecular condensates from simulations of spinodal decomposition

Fundamental Aspects of Phase-Separated Biomolecular Condensates

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