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Title: Relation between single-molecule properties and phase behavior of intrinsically disordered proteins

Abstract

Proteins that undergo liquid–liquid phase separation (LLPS) have been shown to play a critical role in many physiological functions through formation of condensed liquid-like assemblies that function as membraneless organelles within biological systems. To understand how different proteins may contribute differently to these assemblies and their functions, it is important to understand the molecular driving forces of phase separation and characterize their phase boundaries and material properties. Experimental studies have shown that intrinsically disordered regions of these proteins are a major driving force, as many of them undergo LLPS in isolation. Previous work on polymer solution phase behavior suggests a potential correspondence between intramolecular and intermolecular interactions that can be leveraged to discover relationships between single-molecule properties and phase boundaries. Here, we take advantage of a recently developed coarse-grained framework to calculate the θ temperature T θ , the Boyle temperature T B , and the critical temperature T c for 20 diverse protein sequences, and we show that these three properties are highly correlated. We also highlight that these correlations are not specific to our model or simulation methodology by comparing between different pairwise potentials and with data from other work. We, therefore, suggest that smaller simulations or experiments to determine T θ or T B can provide useful insights into the corresponding phase behavior.

Authors:
; ; ORCiD logo; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States); Lehigh Univ., Bethlehem, PA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1470803
Alternate Identifier(s):
OSTI ID: 1543910
Grant/Contract Number:  
SC001397; AC02-05CH11231; SC0013979
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 40; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Science & Technology; Other Topics; membraneless organelles; liquid–liquid phase separation; intrinsically disordered proteins

Citation Formats

Dignon, Gregory L., Zheng, Wenwei, Best, Robert B., Kim, Young C., and Mittal, Jeetain. Relation between single-molecule properties and phase behavior of intrinsically disordered proteins. United States: N. p., 2018. Web. doi:10.1073/pnas.1804177115.
Dignon, Gregory L., Zheng, Wenwei, Best, Robert B., Kim, Young C., & Mittal, Jeetain. Relation between single-molecule properties and phase behavior of intrinsically disordered proteins. United States. doi:10.1073/pnas.1804177115.
Dignon, Gregory L., Zheng, Wenwei, Best, Robert B., Kim, Young C., and Mittal, Jeetain. Fri . "Relation between single-molecule properties and phase behavior of intrinsically disordered proteins". United States. doi:10.1073/pnas.1804177115.
@article{osti_1470803,
title = {Relation between single-molecule properties and phase behavior of intrinsically disordered proteins},
author = {Dignon, Gregory L. and Zheng, Wenwei and Best, Robert B. and Kim, Young C. and Mittal, Jeetain},
abstractNote = {Proteins that undergo liquid–liquid phase separation (LLPS) have been shown to play a critical role in many physiological functions through formation of condensed liquid-like assemblies that function as membraneless organelles within biological systems. To understand how different proteins may contribute differently to these assemblies and their functions, it is important to understand the molecular driving forces of phase separation and characterize their phase boundaries and material properties. Experimental studies have shown that intrinsically disordered regions of these proteins are a major driving force, as many of them undergo LLPS in isolation. Previous work on polymer solution phase behavior suggests a potential correspondence between intramolecular and intermolecular interactions that can be leveraged to discover relationships between single-molecule properties and phase boundaries. Here, we take advantage of a recently developed coarse-grained framework to calculate the θ temperature T θ , the Boyle temperature T B , and the critical temperature T c for 20 diverse protein sequences, and we show that these three properties are highly correlated. We also highlight that these correlations are not specific to our model or simulation methodology by comparing between different pairwise potentials and with data from other work. We, therefore, suggest that smaller simulations or experiments to determine T θ or T B can provide useful insights into the corresponding phase behavior.},
doi = {10.1073/pnas.1804177115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 40,
volume = 115,
place = {United States},
year = {2018},
month = {9}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1073/pnas.1804177115

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Cited by: 13 works
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