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

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...

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Autores principales: Qin, Sanbo, Zhou, Huan-Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168431/
https://www.ncbi.nlm.nih.gov/pubmed/37162827
http://dx.doi.org/10.1101/2023.04.25.538329
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author Qin, Sanbo
Zhou, Huan-Xiang
author_facet Qin, Sanbo
Zhou, Huan-Xiang
author_sort Qin, Sanbo
collection PubMed
description 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 [Formula: see text]. We obtain a higher [Formula: see text] for a known high- [Formula: see text] γ-crystallin, γF, than for a low- [Formula: see text] paralog, γB. The difference in [Formula: see text] is 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 [Formula: see text]. 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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spelling pubmed-101684312023-05-10 Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence Qin, Sanbo Zhou, Huan-Xiang bioRxiv Article 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 [Formula: see text]. We obtain a higher [Formula: see text] for a known high- [Formula: see text] γ-crystallin, γF, than for a low- [Formula: see text] paralog, γB. The difference in [Formula: see text] is 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 [Formula: see text]. This type of analysis enables us to link phase equilibrium to amino-acid sequence and to design mutations for altering phase equilibrium. Cold Spring Harbor Laboratory 2023-04-28 /pmc/articles/PMC10168431/ /pubmed/37162827 http://dx.doi.org/10.1101/2023.04.25.538329 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Qin, Sanbo
Zhou, Huan-Xiang
Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence
title Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence
title_full Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence
title_fullStr Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence
title_full_unstemmed Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence
title_short Atomistic Modeling of Liquid-Liquid Phase Equilibrium Explains Dependence of Critical Temperature on γ-Crystallin Sequence
title_sort atomistic modeling of liquid-liquid phase equilibrium explains dependence of critical temperature on γ-crystallin sequence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10168431/
https://www.ncbi.nlm.nih.gov/pubmed/37162827
http://dx.doi.org/10.1101/2023.04.25.538329
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